Conference Coverage

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

PHOENIX – Open-label extension studies of two neonatal Fc receptor–blocking antibodies showed good safety and efficacy in patients with myasthenia gravis (MG). The two drugs, rozanolixizumab (Rystiggo, UCB) and efgartigimod PH20 (Vyvgart, Argenx SE), received Food and Drug Administration approval in June 2023 and December 2021, respectively, for the treatment of MG.

The neonatal Fc receptor binds to IgG within cells and recycles it back into the blood, leading to increased serum levels. The antibodies bind to the neonatal Fc receptor and promote its degradation, therefore preventing IgG recycling without interfering with its production. They do not affect the levels of other immunoglobulin isotypes.

At the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM), researchers presented data from an open-label extension study following the phase 3 MycarinG trial of rozanolixizumab and the ADAPT-SC+ study of efgartigimod.

In the MycarinG study, rozanolixizumab “showed both statistically significant and clinically meaningful improvements in multiple endpoints,” said Vera Bril, MD, during a presentation of the results.

Rozanolixizumab is approved for MG patients who are anti–acetylcholine receptor (AchR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive. Efgartigimod is approved for MG patients who are AChR positive.

After completing MycarinG, patients were eligible to enroll in one of two open-label studies, one of each dose.

The new efficacy analysis focused on 110 patients who underwent two or more consecutive symptom-driven treatment cycles. A safety analysis focused on 188 patients who received at least one cycle of treatment.

“The post hoc analysis showed that the clinically meaningful improvements in the generalized myasthenia gravis symptoms were maintained over time for the cohort across rozanolixizumab cycles, while individual patients move through the consecutive treatment cycles, rozanolixizumab had an acceptable safety profile that was maintained across repeated treatments cycles. This is consistent with previous results of rozanolixizumab,” said Dr. Bril, who is a clinical investigator at University of Toronto
 

A reduction in steroid use?

During the Q&A session, George Small, MD, asked if the study had shown a reduction in steroid use among patients with MG.

As clinical associate director of neurology at Allegheny Medical Center, Pittsburgh, he has overseen the care of several hundred patients with generalized MG, as well as participated in clinical trials. “Many physicians use steroids for very quick responses in their patients. I love steroids and I hate steroids. I’ve helped save people’s lives with them, but I’ve also probably hastened their demise, unfortunately, because of the long-term side effects of the medications. Many neurologists in the community will over-utilize steroids because they don’t have access to these more expensive therapies. I look forward to both using these medications more as they become FDA approved and being an advocate for them, because it is my belief that they help decrease the use of steroids,” said Dr. Small in an interview.

Even if new medications do reduce steroid use, there remains a hurdle with insurance companies. “I’ve felt I’ve been forced to use treatments that I know may not be efficacious in the short term in order to get authorization for more expensive therapies that I use now. I’ve had patients admitted to the hospital as I’ve tried to jump through hoops that the insurance companies demanded,” said Dr. Small.
 

Clinical improvements seen

In the MycarinG study, patients received weekly injections of 7 mg/kg, 10 mg/kg rozanolixizumab, or placebo over a 6-week period. Both treatment groups had reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.

MG-ADL and Quantitative Myasthenia Gravis (QMG) scores were consistent across treatment cycles. The mean MG-ADL score dropped by about 4 points at week 6. At around week 10, the mean improvement declined to 2 points, and then by week 14 it increased to 3 points, where it remained consistent out to 50 weeks. A similar pattern was seen in QMG scores, with an approximate 5-point drop at 6 weeks, then about a 1.5-point improvement at 10 weeks, then a mean decrease of around 4 points that stayed stable out to 50 weeks.

Over all cycles of treatment, 89.9% of patients experienced a treatment-emergent adverse event, including 22.3% who had a serious TEAE; the study dropout rate because of TEAEs was 15.4%.

In the ADAPT-SC study, 110 patients were randomized to 10 mg/kg intravenous efgartigimod or 1,000 mg efgartigimod PH20, which is formulated with recombinant human hyaluronidase to allow for rapid administration of larger volumes. After completion of ADAPT-SC, 105 patients from both groups and an additional 79 patients entered the open-label extension study with 1,000 mg efgartigimod PH20.

The study included 141 patients who were AChR-Ab positive and 38 who were AChR-Ab negative. In the first cycle, 34.6% experienced an injection-site reaction, which steadily dropped to 11.5% by the sixth cycle. After each cycle of treatment, the mean change in MG-ADL from study baseline at week 4 was between 4.1 and 4.7 points. The mean change in Myasthenia Gravis Quality of Life 15-Item Questionnaire revisited from study baseline at week 4 was between 5.1 and 6.5 points. The mean change in EuroQoL 5-dimension, 5-level visual analog scale was between 12.3 and 16.0 points at week 4.

MyCarinG was funded by UCB Pharma. ADAPT-SC was funded by Argenx SE. Dr. Bril has financial relationships with Behring, Argenyx, Alexion, Immunovant, Alnylam, Akcea, Takeda, Sanofi, Ionis, Roche, Novo Nordisk, Octapharma, Momenta, Pfizer, CSL Behring, Grifols, Powell Mansfield, UCB, and Viela Bio. Dr. Small is on the speaker’s bureau for Alexion.

NEW YORK – Treated with chimeric antigen receptor (CAR) T-cell therapy, most patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) achieved better outcomes than those receiving autologous stem cell transplants (ASCT), according to evidence presented at the 2023 Lymphoma, Leukemia, and Myeloma Congress.

DLBCL is characterized by the National Institutes of Health as an aggressive malignancy and the most common lymphoma. Research presented at the conference indicated that 60%70% of patients were cured with six to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP).

courtesy MD Anderson Cancer Center

“In the past, if a relapsed of refractory DLBCL patient couldn’t get a transplant, they were likely headed for palliative care. CAR T-cell therapy is no longer experimental. Not only can we offer it to patients who are ineligible for transplant (and manage the side effects), the treatment has proven to offer better overall survival and cure rates, even in patients who eligible for ASCT,” said presenter Jason Westin, MD, director of the lymphoma clinical research program at the University of Texas MD Anderson Cancer Center, Houston.

The ZUMA-7 phase 3trial among patients with early r/r DLBCL demonstrated the superiority of CAR T-cell therapy with the agent, axicabtagene ciloleucel (YESCARTA, Kita Pharma) versus standard of care (chemoimmunotherapy followed by high-dose chemotherapy and ASCT). Those in the axicabtagene ciloleucel (axi-cel) group had a median progression free survival (PFS) of 14.7 months and an estimated 4-year overall survival (OS) rate of 54.6% compared to 3.7 months and 46% in the control group.

Patients treated with axi-cel experienced a higher rate of adverse events (AE) grade 3 of higher, compared with the ACST group (91% vs. 83%) Furthermore, patients who received axi-cel had cytokine release syndrome (6%) and neurologic events in (21%) grade 3 or higher, compared with 0% and less than 1% in the ASCT group.

At the conference, Dr. Westin’s copanelist Jennifer Amengual, MD, of Columbia University Irving Medical Center, New York, interpreted the data on adverse events (AEs) from ZUMA-7 to mean that if a patient is especially susceptible to CAR T side effects, then ASCT could be preferred. She also outlined a second strategy that shows promise when a patient has either failed CAR T and ASCT or whose frailty demands an approach that avoids AEs.

Dr. Amengual cited a study in which patients with r/r DLBCL were treated with the bispecific antibody glofitamab (Columvi/Roche), which induced a complete response in 39% of patients at a median follow-up of 12.6 months and a 12-month PFS rate of 37%. Those treated with the agent experienced cytokine release syndrome and neurologic events grade 3 or higher, at a rate of 4% and 3% respectively.

“Efforts to make off-the-shelf CAR T therapy are ongoing. With some fine-tuning the PFS and OS with bispecific antibodies will likely approach or exceed both CAR T and ACST. The fact that they could come right off the shelf, rather than having to be tailor made for each patient, gives them a huge advantage in terms of cost and availability, while maintaining what appears to be an excellent safety profile” said Morton Colman, MD, professor of medicine at Weill Cornell Medicine, New York, and chair of the 2023 Lymphoma, Leukemia, and Myeloma Congress.

Dr. Amengual disclosed ties with Astra Zeneca and Incyte. Dr. Westin reported ties with Abbie, ADC therapeutics, AstraZeneca, Bristol-Myers Squibb, Genentech, GenMad, Hanssen, Kite/Gilead, Morphosys/Incyte, Novartis, Nurix, Regeneron, and SeaGen. Dr. Coleman had no disclosures.

NEW YORK – Treated with chimeric antigen receptor (CAR) T-cell therapy, most patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) achieved better outcomes than those receiving autologous stem cell transplants (ASCT), according to evidence presented at the 2023 Lymphoma, Leukemia, and Myeloma Congress.

DLBCL is characterized by the National Institutes of Health as an aggressive malignancy and the most common lymphoma. Research presented at the conference indicated that 60%70% of patients were cured with six to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP).

courtesy MD Anderson Cancer Center

“In the past, if a relapsed of refractory DLBCL patient couldn’t get a transplant, they were likely headed for palliative care. CAR T-cell therapy is no longer experimental. Not only can we offer it to patients who are ineligible for transplant (and manage the side effects), the treatment has proven to offer better overall survival and cure rates, even in patients who eligible for ASCT,” said presenter Jason Westin, MD, director of the lymphoma clinical research program at the University of Texas MD Anderson Cancer Center, Houston.

The ZUMA-7 phase 3trial among patients with early r/r DLBCL demonstrated the superiority of CAR T-cell therapy with the agent, axicabtagene ciloleucel (YESCARTA, Kita Pharma) versus standard of care (chemoimmunotherapy followed by high-dose chemotherapy and ASCT). Those in the axicabtagene ciloleucel (axi-cel) group had a median progression free survival (PFS) of 14.7 months and an estimated 4-year overall survival (OS) rate of 54.6% compared to 3.7 months and 46% in the control group.

Patients treated with axi-cel experienced a higher rate of adverse events (AE) grade 3 of higher, compared with the ACST group (91% vs. 83%) Furthermore, patients who received axi-cel had cytokine release syndrome (6%) and neurologic events in (21%) grade 3 or higher, compared with 0% and less than 1% in the ASCT group.

At the conference, Dr. Westin’s copanelist Jennifer Amengual, MD, of Columbia University Irving Medical Center, New York, interpreted the data on adverse events (AEs) from ZUMA-7 to mean that if a patient is especially susceptible to CAR T side effects, then ASCT could be preferred. She also outlined a second strategy that shows promise when a patient has either failed CAR T and ASCT or whose frailty demands an approach that avoids AEs.

Dr. Amengual cited a study in which patients with r/r DLBCL were treated with the bispecific antibody glofitamab (Columvi/Roche), which induced a complete response in 39% of patients at a median follow-up of 12.6 months and a 12-month PFS rate of 37%. Those treated with the agent experienced cytokine release syndrome and neurologic events grade 3 or higher, at a rate of 4% and 3% respectively.

“Efforts to make off-the-shelf CAR T therapy are ongoing. With some fine-tuning the PFS and OS with bispecific antibodies will likely approach or exceed both CAR T and ACST. The fact that they could come right off the shelf, rather than having to be tailor made for each patient, gives them a huge advantage in terms of cost and availability, while maintaining what appears to be an excellent safety profile” said Morton Colman, MD, professor of medicine at Weill Cornell Medicine, New York, and chair of the 2023 Lymphoma, Leukemia, and Myeloma Congress.

Dr. Amengual disclosed ties with Astra Zeneca and Incyte. Dr. Westin reported ties with Abbie, ADC therapeutics, AstraZeneca, Bristol-Myers Squibb, Genentech, GenMad, Hanssen, Kite/Gilead, Morphosys/Incyte, Novartis, Nurix, Regeneron, and SeaGen. Dr. Coleman had no disclosures.

NEW YORK – Treated with chimeric antigen receptor (CAR) T-cell therapy, most patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) achieved better outcomes than those receiving autologous stem cell transplants (ASCT), according to evidence presented at the 2023 Lymphoma, Leukemia, and Myeloma Congress.

DLBCL is characterized by the National Institutes of Health as an aggressive malignancy and the most common lymphoma. Research presented at the conference indicated that 60%70% of patients were cured with six to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP).

courtesy MD Anderson Cancer Center

“In the past, if a relapsed of refractory DLBCL patient couldn’t get a transplant, they were likely headed for palliative care. CAR T-cell therapy is no longer experimental. Not only can we offer it to patients who are ineligible for transplant (and manage the side effects), the treatment has proven to offer better overall survival and cure rates, even in patients who eligible for ASCT,” said presenter Jason Westin, MD, director of the lymphoma clinical research program at the University of Texas MD Anderson Cancer Center, Houston.

The ZUMA-7 phase 3trial among patients with early r/r DLBCL demonstrated the superiority of CAR T-cell therapy with the agent, axicabtagene ciloleucel (YESCARTA, Kita Pharma) versus standard of care (chemoimmunotherapy followed by high-dose chemotherapy and ASCT). Those in the axicabtagene ciloleucel (axi-cel) group had a median progression free survival (PFS) of 14.7 months and an estimated 4-year overall survival (OS) rate of 54.6% compared to 3.7 months and 46% in the control group.

Patients treated with axi-cel experienced a higher rate of adverse events (AE) grade 3 of higher, compared with the ACST group (91% vs. 83%) Furthermore, patients who received axi-cel had cytokine release syndrome (6%) and neurologic events in (21%) grade 3 or higher, compared with 0% and less than 1% in the ASCT group.

At the conference, Dr. Westin’s copanelist Jennifer Amengual, MD, of Columbia University Irving Medical Center, New York, interpreted the data on adverse events (AEs) from ZUMA-7 to mean that if a patient is especially susceptible to CAR T side effects, then ASCT could be preferred. She also outlined a second strategy that shows promise when a patient has either failed CAR T and ASCT or whose frailty demands an approach that avoids AEs.

Dr. Amengual cited a study in which patients with r/r DLBCL were treated with the bispecific antibody glofitamab (Columvi/Roche), which induced a complete response in 39% of patients at a median follow-up of 12.6 months and a 12-month PFS rate of 37%. Those treated with the agent experienced cytokine release syndrome and neurologic events grade 3 or higher, at a rate of 4% and 3% respectively.

“Efforts to make off-the-shelf CAR T therapy are ongoing. With some fine-tuning the PFS and OS with bispecific antibodies will likely approach or exceed both CAR T and ACST. The fact that they could come right off the shelf, rather than having to be tailor made for each patient, gives them a huge advantage in terms of cost and availability, while maintaining what appears to be an excellent safety profile” said Morton Colman, MD, professor of medicine at Weill Cornell Medicine, New York, and chair of the 2023 Lymphoma, Leukemia, and Myeloma Congress.

Dr. Amengual disclosed ties with Astra Zeneca and Incyte. Dr. Westin reported ties with Abbie, ADC therapeutics, AstraZeneca, Bristol-Myers Squibb, Genentech, GenMad, Hanssen, Kite/Gilead, Morphosys/Incyte, Novartis, Nurix, Regeneron, and SeaGen. Dr. Coleman had no disclosures.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COPENHAGEN – People with precancerous colonic lesions show significant differences in their gut microbiome, compared with the general population up to 5 years before the lesions develop, according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.

The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.

“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.

The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.

In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.

“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%. 

“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
 

Longitudinal analysis using large Dutch databases

To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.

They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.

“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained. 

The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
 

More precancerous lesions found after fecal sampling

There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.

Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.

When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.

The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.

“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.

Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.

“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
 

More time needed

Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.

“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”

He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.” 

However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.

Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nemolizumab is gearing up to be a potential new treatment for prurigo nodularis, with further phase 3 data supporting its efficacy and safety reported at the annual Congress of the European Academy of Dermatology and Venereology.

In the OLYMPIA 1 study, clinically significant improvements in both itch and skin lesions were seen after 16 weeks of treatment with nemolizumab compared with placebo (P < .0001).

Indeed, among the 286 patients who participated in the trial (190 on nemolizumab and 96 on placebo), 58.4% of those treated with nemolizumab and 16.7% of those who received placebo had an improvement of 4 points or more in the weekly average peak pruritus numeric rating scale (PP-NRS) at week 16 (P < .0001).

Skin lesions were assessed using an investigators general assessment (IGA) score, where IGA success was defined as a score of 0/1 indicating clear or almost clear skin or where there had been at least a 2-point change from baseline values. Over a quarter (26.3%) of nemolizumab-treated patients met these criteria versus 7.3% for those on placebo (P = .0001).

“These results confirm the results of the OLYMPIA 2 study, the other phase 3 study, and now I hope you understand why we are so excited,” lead investigator Sonja Ständer, MD, of the Center for Chronic Pruritus at University Hospital Münster, Germany, said at the meeting, where she presented the data.

The OLYMPIA 2 study included 274 patients and the results showed a weekly average PP-NRS score improvement of 56.3% vs. 20.9% for placebo and IGA success in 37.7% and 11% of patients, respectively, at 16 weeks.
 

First-in-class therapy

“We know how difficult it is to treat patients; they are refractory to treatment, frustrated, and this really impacts them regarding their quality of life,” said Dr. Ständer. New options are needed to help patients, and nemolizumab, a first-in-class interleukin-31 (IL-31) receptor alpha antagonist, is one treatment that may answer this call.

Prurigo nodularis is a chronic neuroimmune skin condition characterized by severe itch and multiple nodular skin lesions, Dr. Ständer explained. She added that there is evidence that IL-31 has a key role to play in the development of itch, and in differentiation of keratinocytes, type 2 and type 17 immune responses, and fibrosis associated with the condition.

The OLYMPIA 1 and 2 trials are part of a large developmental program that includes two ongoing trials. One is assessing the durability of response over 24 weeks in 40 patients and the other is a long-term extension trial involving 450 patients from the OLYMPIA 1 and 2 trials.
 

Inclusion criteria and additional results

For inclusion in the study, adults with prurigo nodularis for at least 6 months had to have 20 or more nodules on the body with a bilateral distribution, an IGA score of 3 or more, and an average PP-NRS of 7 or higher. The latter “was really a high bar for them to qualify for the trial,” said Dr. Ständer.

After an initial 4-week screening period, patients were randomly assigned to 24 weeks of treatment with nemolizumab or placebo given as a subcutaneous injection every 4 weeks. An 8-week “off-treatment” period followed.

The nemolizumab dose was based on the patient’s body weight, with patients weighing less than 90 kg (198 pounds) getting a loading dose of 60 mg followed by further doses of 30 mg; while patients weighing 90 kg or more receiving 50 mg of nemolizumab. 

Dr. Ständer reported that nemolizumab met all of the trials’ secondary endpoints; this included at least a 4-point improvement in sleep disturbance. She noted that changes in itch and subsequent sleep disturbance occurred early, at 4 weeks of treatment – after just one injection of nemolizumab.

The response rates seen in the moderate to severe prurigo nodularis population studies are quite unique when compared with conventional therapies, Dr. Ständer maintained. “We’ve never seen something like this before.”
 

No safety concerns

No significant difference in tolerability was seen between the nemolizumab and placebo groups, Dr. Ständer observed. Any adverse event occurred in 71.7% and 65.3% of patients, respectively, and serious adverse events in 8.6% and 10.5%.

There was a similar rate of adverse events leading to discontinuation, respectively (4.8% vs. 4.2%).

Headache was seen more frequently among those on nemolizumab than those on placebo (7.0% vs. 2.1%), and there was a higher number of eczema cases among those on nemolizumab (5.3% vs. 1.1%). The latter is somewhat paradoxical because nemolizumab is also being studied as a treatment for atopic dermatitis, with good results seen in phase 3 trials. Asked about this finding after her presentation, Dr. Ständer said “we are following up on that to know exactly what is going on; this is a side effect of nemolizumab that is seen also with other biologics.”
 

JAK inhibitor trial for PN, CPUO

Nemolizumab is not the only promising new approach to treating prurigo nodularis. During a separate late-breaking news session at the meeting, Shawn Kwatra, MD, director of the Johns Hopkins Itch Center in Baltimore, presented “dramatic” data from a “proof-of-concept” phase 2 study with the Janus kinase (JAK) inhibitor abrocitinib (Cibinqo), which is approved for atopic dermatitis in the United States and Europe.

The investigator-initiated trial took a different approach from most other trials, Dr. Kwatra said. The starting point was to look at studying multiple rather than single dermatologic diseases that were perhaps being left a little by the wayside but may share some common ground. Those two diseases were prurigo nodularis and chronic pruritus of unknown origin (CPUO).

“They’re actually very analogous conditions in the way we treat, so I thought those would be a good pair,” Dr. Kwatra said, noting that there were several studies that made him think that JAK inhibition “would be an interesting concept to try.”

On that basis, 10 women with prurigo nodularis (mean age, 58 years) and two women and eight men with CPUO (mean age, 70 years) were recruited and all were treated with abrocitinib at a once-daily oral dose of 200 mg for 12 weeks.

“They all had really intense itch,” before treatment, Dr. Kwatra said. The mean baseline PP-NRS was 9.2 and 8.2 in the prurigo nodularis and CPUO groups, respectively. By the end of treatment, however, “the improvement in itch was pretty dramatic,” especially for prurigo nodularis, he said.

At 12 weeks, the PP-NRS score had fallen to 2.0 in the prurigo nodularis group, equating to a significant 78% change from baseline (P < .001). And, in the CPUO group, the 12-week PP-NRS score was 3.8, nearly a 54% drop from baseline (P = .01).

Sleep disturbance was improved for both conditions, and in the patients with prurigo nodularis, there were improvements in skin lesions. Looking at the patients who responded to treatment, Dr. Kwatra noted that “if you responded, you respond fast, and you respond almost entirely.”

Additional findings from cutaneous transcriptome analysis showed that JAK inhibition with abrocitinib was modulating Th1-, Th2-, Th17-, and Th22-mediated pathways in both groups of patients.

The overall frequency of adverse events was low, and no serious adverse events occurred.

Commenting on the potential use of abrocitinib in managing patients with PN and CPUO, Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, told this news organization that JAK1 inhibitors “are showing promising results in treating several diseases.”

Dr. Matos, who was not involved in the study, added that JAK inhibition was “of special interest in prurigo nodularis and chronic pruritus, since these are some of the most difficult diseases to treat with limited therapeutic options.”

Dr. Kwatra observed: “Obviously, we need further development. But we also have clues here about how to design phase 3 trials.”

Galderma funded the OLYMPIA 1 and 2 studies. Dr. Ständer was an investigator for the trial and reported serving as a consultant, speaker, or investigator for multiple pharmaceutical companies, including Galderma.

Johns Hopkins University supported the abrocitinib study with funding from Pfizer. Dr. Kwatra is an advisory board member or consultant to several pharmaceutical companies and is an investigator for Galderma, Incyte, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

Nemolizumab is gearing up to be a potential new treatment for prurigo nodularis, with further phase 3 data supporting its efficacy and safety reported at the annual Congress of the European Academy of Dermatology and Venereology.

In the OLYMPIA 1 study, clinically significant improvements in both itch and skin lesions were seen after 16 weeks of treatment with nemolizumab compared with placebo (P < .0001).

Indeed, among the 286 patients who participated in the trial (190 on nemolizumab and 96 on placebo), 58.4% of those treated with nemolizumab and 16.7% of those who received placebo had an improvement of 4 points or more in the weekly average peak pruritus numeric rating scale (PP-NRS) at week 16 (P < .0001).

Skin lesions were assessed using an investigators general assessment (IGA) score, where IGA success was defined as a score of 0/1 indicating clear or almost clear skin or where there had been at least a 2-point change from baseline values. Over a quarter (26.3%) of nemolizumab-treated patients met these criteria versus 7.3% for those on placebo (P = .0001).

“These results confirm the results of the OLYMPIA 2 study, the other phase 3 study, and now I hope you understand why we are so excited,” lead investigator Sonja Ständer, MD, of the Center for Chronic Pruritus at University Hospital Münster, Germany, said at the meeting, where she presented the data.

The OLYMPIA 2 study included 274 patients and the results showed a weekly average PP-NRS score improvement of 56.3% vs. 20.9% for placebo and IGA success in 37.7% and 11% of patients, respectively, at 16 weeks.
 

First-in-class therapy

“We know how difficult it is to treat patients; they are refractory to treatment, frustrated, and this really impacts them regarding their quality of life,” said Dr. Ständer. New options are needed to help patients, and nemolizumab, a first-in-class interleukin-31 (IL-31) receptor alpha antagonist, is one treatment that may answer this call.

Prurigo nodularis is a chronic neuroimmune skin condition characterized by severe itch and multiple nodular skin lesions, Dr. Ständer explained. She added that there is evidence that IL-31 has a key role to play in the development of itch, and in differentiation of keratinocytes, type 2 and type 17 immune responses, and fibrosis associated with the condition.

The OLYMPIA 1 and 2 trials are part of a large developmental program that includes two ongoing trials. One is assessing the durability of response over 24 weeks in 40 patients and the other is a long-term extension trial involving 450 patients from the OLYMPIA 1 and 2 trials.
 

Inclusion criteria and additional results

For inclusion in the study, adults with prurigo nodularis for at least 6 months had to have 20 or more nodules on the body with a bilateral distribution, an IGA score of 3 or more, and an average PP-NRS of 7 or higher. The latter “was really a high bar for them to qualify for the trial,” said Dr. Ständer.

After an initial 4-week screening period, patients were randomly assigned to 24 weeks of treatment with nemolizumab or placebo given as a subcutaneous injection every 4 weeks. An 8-week “off-treatment” period followed.

The nemolizumab dose was based on the patient’s body weight, with patients weighing less than 90 kg (198 pounds) getting a loading dose of 60 mg followed by further doses of 30 mg; while patients weighing 90 kg or more receiving 50 mg of nemolizumab. 

Dr. Ständer reported that nemolizumab met all of the trials’ secondary endpoints; this included at least a 4-point improvement in sleep disturbance. She noted that changes in itch and subsequent sleep disturbance occurred early, at 4 weeks of treatment – after just one injection of nemolizumab.

The response rates seen in the moderate to severe prurigo nodularis population studies are quite unique when compared with conventional therapies, Dr. Ständer maintained. “We’ve never seen something like this before.”
 

No safety concerns

No significant difference in tolerability was seen between the nemolizumab and placebo groups, Dr. Ständer observed. Any adverse event occurred in 71.7% and 65.3% of patients, respectively, and serious adverse events in 8.6% and 10.5%.

There was a similar rate of adverse events leading to discontinuation, respectively (4.8% vs. 4.2%).

Headache was seen more frequently among those on nemolizumab than those on placebo (7.0% vs. 2.1%), and there was a higher number of eczema cases among those on nemolizumab (5.3% vs. 1.1%). The latter is somewhat paradoxical because nemolizumab is also being studied as a treatment for atopic dermatitis, with good results seen in phase 3 trials. Asked about this finding after her presentation, Dr. Ständer said “we are following up on that to know exactly what is going on; this is a side effect of nemolizumab that is seen also with other biologics.”
 

JAK inhibitor trial for PN, CPUO

Nemolizumab is not the only promising new approach to treating prurigo nodularis. During a separate late-breaking news session at the meeting, Shawn Kwatra, MD, director of the Johns Hopkins Itch Center in Baltimore, presented “dramatic” data from a “proof-of-concept” phase 2 study with the Janus kinase (JAK) inhibitor abrocitinib (Cibinqo), which is approved for atopic dermatitis in the United States and Europe.

The investigator-initiated trial took a different approach from most other trials, Dr. Kwatra said. The starting point was to look at studying multiple rather than single dermatologic diseases that were perhaps being left a little by the wayside but may share some common ground. Those two diseases were prurigo nodularis and chronic pruritus of unknown origin (CPUO).

“They’re actually very analogous conditions in the way we treat, so I thought those would be a good pair,” Dr. Kwatra said, noting that there were several studies that made him think that JAK inhibition “would be an interesting concept to try.”

On that basis, 10 women with prurigo nodularis (mean age, 58 years) and two women and eight men with CPUO (mean age, 70 years) were recruited and all were treated with abrocitinib at a once-daily oral dose of 200 mg for 12 weeks.

“They all had really intense itch,” before treatment, Dr. Kwatra said. The mean baseline PP-NRS was 9.2 and 8.2 in the prurigo nodularis and CPUO groups, respectively. By the end of treatment, however, “the improvement in itch was pretty dramatic,” especially for prurigo nodularis, he said.

At 12 weeks, the PP-NRS score had fallen to 2.0 in the prurigo nodularis group, equating to a significant 78% change from baseline (P < .001). And, in the CPUO group, the 12-week PP-NRS score was 3.8, nearly a 54% drop from baseline (P = .01).

Sleep disturbance was improved for both conditions, and in the patients with prurigo nodularis, there were improvements in skin lesions. Looking at the patients who responded to treatment, Dr. Kwatra noted that “if you responded, you respond fast, and you respond almost entirely.”

Additional findings from cutaneous transcriptome analysis showed that JAK inhibition with abrocitinib was modulating Th1-, Th2-, Th17-, and Th22-mediated pathways in both groups of patients.

The overall frequency of adverse events was low, and no serious adverse events occurred.

Commenting on the potential use of abrocitinib in managing patients with PN and CPUO, Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, told this news organization that JAK1 inhibitors “are showing promising results in treating several diseases.”

Dr. Matos, who was not involved in the study, added that JAK inhibition was “of special interest in prurigo nodularis and chronic pruritus, since these are some of the most difficult diseases to treat with limited therapeutic options.”

Dr. Kwatra observed: “Obviously, we need further development. But we also have clues here about how to design phase 3 trials.”

Galderma funded the OLYMPIA 1 and 2 studies. Dr. Ständer was an investigator for the trial and reported serving as a consultant, speaker, or investigator for multiple pharmaceutical companies, including Galderma.

Johns Hopkins University supported the abrocitinib study with funding from Pfizer. Dr. Kwatra is an advisory board member or consultant to several pharmaceutical companies and is an investigator for Galderma, Incyte, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

Nemolizumab is gearing up to be a potential new treatment for prurigo nodularis, with further phase 3 data supporting its efficacy and safety reported at the annual Congress of the European Academy of Dermatology and Venereology.

In the OLYMPIA 1 study, clinically significant improvements in both itch and skin lesions were seen after 16 weeks of treatment with nemolizumab compared with placebo (P < .0001).

Indeed, among the 286 patients who participated in the trial (190 on nemolizumab and 96 on placebo), 58.4% of those treated with nemolizumab and 16.7% of those who received placebo had an improvement of 4 points or more in the weekly average peak pruritus numeric rating scale (PP-NRS) at week 16 (P < .0001).

Skin lesions were assessed using an investigators general assessment (IGA) score, where IGA success was defined as a score of 0/1 indicating clear or almost clear skin or where there had been at least a 2-point change from baseline values. Over a quarter (26.3%) of nemolizumab-treated patients met these criteria versus 7.3% for those on placebo (P = .0001).

“These results confirm the results of the OLYMPIA 2 study, the other phase 3 study, and now I hope you understand why we are so excited,” lead investigator Sonja Ständer, MD, of the Center for Chronic Pruritus at University Hospital Münster, Germany, said at the meeting, where she presented the data.

The OLYMPIA 2 study included 274 patients and the results showed a weekly average PP-NRS score improvement of 56.3% vs. 20.9% for placebo and IGA success in 37.7% and 11% of patients, respectively, at 16 weeks.
 

First-in-class therapy

“We know how difficult it is to treat patients; they are refractory to treatment, frustrated, and this really impacts them regarding their quality of life,” said Dr. Ständer. New options are needed to help patients, and nemolizumab, a first-in-class interleukin-31 (IL-31) receptor alpha antagonist, is one treatment that may answer this call.

Prurigo nodularis is a chronic neuroimmune skin condition characterized by severe itch and multiple nodular skin lesions, Dr. Ständer explained. She added that there is evidence that IL-31 has a key role to play in the development of itch, and in differentiation of keratinocytes, type 2 and type 17 immune responses, and fibrosis associated with the condition.

The OLYMPIA 1 and 2 trials are part of a large developmental program that includes two ongoing trials. One is assessing the durability of response over 24 weeks in 40 patients and the other is a long-term extension trial involving 450 patients from the OLYMPIA 1 and 2 trials.
 

Inclusion criteria and additional results

For inclusion in the study, adults with prurigo nodularis for at least 6 months had to have 20 or more nodules on the body with a bilateral distribution, an IGA score of 3 or more, and an average PP-NRS of 7 or higher. The latter “was really a high bar for them to qualify for the trial,” said Dr. Ständer.

After an initial 4-week screening period, patients were randomly assigned to 24 weeks of treatment with nemolizumab or placebo given as a subcutaneous injection every 4 weeks. An 8-week “off-treatment” period followed.

The nemolizumab dose was based on the patient’s body weight, with patients weighing less than 90 kg (198 pounds) getting a loading dose of 60 mg followed by further doses of 30 mg; while patients weighing 90 kg or more receiving 50 mg of nemolizumab. 

Dr. Ständer reported that nemolizumab met all of the trials’ secondary endpoints; this included at least a 4-point improvement in sleep disturbance. She noted that changes in itch and subsequent sleep disturbance occurred early, at 4 weeks of treatment – after just one injection of nemolizumab.

The response rates seen in the moderate to severe prurigo nodularis population studies are quite unique when compared with conventional therapies, Dr. Ständer maintained. “We’ve never seen something like this before.”
 

No safety concerns

No significant difference in tolerability was seen between the nemolizumab and placebo groups, Dr. Ständer observed. Any adverse event occurred in 71.7% and 65.3% of patients, respectively, and serious adverse events in 8.6% and 10.5%.

There was a similar rate of adverse events leading to discontinuation, respectively (4.8% vs. 4.2%).

Headache was seen more frequently among those on nemolizumab than those on placebo (7.0% vs. 2.1%), and there was a higher number of eczema cases among those on nemolizumab (5.3% vs. 1.1%). The latter is somewhat paradoxical because nemolizumab is also being studied as a treatment for atopic dermatitis, with good results seen in phase 3 trials. Asked about this finding after her presentation, Dr. Ständer said “we are following up on that to know exactly what is going on; this is a side effect of nemolizumab that is seen also with other biologics.”
 

JAK inhibitor trial for PN, CPUO

Nemolizumab is not the only promising new approach to treating prurigo nodularis. During a separate late-breaking news session at the meeting, Shawn Kwatra, MD, director of the Johns Hopkins Itch Center in Baltimore, presented “dramatic” data from a “proof-of-concept” phase 2 study with the Janus kinase (JAK) inhibitor abrocitinib (Cibinqo), which is approved for atopic dermatitis in the United States and Europe.

The investigator-initiated trial took a different approach from most other trials, Dr. Kwatra said. The starting point was to look at studying multiple rather than single dermatologic diseases that were perhaps being left a little by the wayside but may share some common ground. Those two diseases were prurigo nodularis and chronic pruritus of unknown origin (CPUO).

“They’re actually very analogous conditions in the way we treat, so I thought those would be a good pair,” Dr. Kwatra said, noting that there were several studies that made him think that JAK inhibition “would be an interesting concept to try.”

On that basis, 10 women with prurigo nodularis (mean age, 58 years) and two women and eight men with CPUO (mean age, 70 years) were recruited and all were treated with abrocitinib at a once-daily oral dose of 200 mg for 12 weeks.

“They all had really intense itch,” before treatment, Dr. Kwatra said. The mean baseline PP-NRS was 9.2 and 8.2 in the prurigo nodularis and CPUO groups, respectively. By the end of treatment, however, “the improvement in itch was pretty dramatic,” especially for prurigo nodularis, he said.

At 12 weeks, the PP-NRS score had fallen to 2.0 in the prurigo nodularis group, equating to a significant 78% change from baseline (P < .001). And, in the CPUO group, the 12-week PP-NRS score was 3.8, nearly a 54% drop from baseline (P = .01).

Sleep disturbance was improved for both conditions, and in the patients with prurigo nodularis, there were improvements in skin lesions. Looking at the patients who responded to treatment, Dr. Kwatra noted that “if you responded, you respond fast, and you respond almost entirely.”

Additional findings from cutaneous transcriptome analysis showed that JAK inhibition with abrocitinib was modulating Th1-, Th2-, Th17-, and Th22-mediated pathways in both groups of patients.

The overall frequency of adverse events was low, and no serious adverse events occurred.

Commenting on the potential use of abrocitinib in managing patients with PN and CPUO, Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, told this news organization that JAK1 inhibitors “are showing promising results in treating several diseases.”

Dr. Matos, who was not involved in the study, added that JAK inhibition was “of special interest in prurigo nodularis and chronic pruritus, since these are some of the most difficult diseases to treat with limited therapeutic options.”

Dr. Kwatra observed: “Obviously, we need further development. But we also have clues here about how to design phase 3 trials.”

Galderma funded the OLYMPIA 1 and 2 studies. Dr. Ständer was an investigator for the trial and reported serving as a consultant, speaker, or investigator for multiple pharmaceutical companies, including Galderma.

Johns Hopkins University supported the abrocitinib study with funding from Pfizer. Dr. Kwatra is an advisory board member or consultant to several pharmaceutical companies and is an investigator for Galderma, Incyte, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

Additional data from the phase 3 EASE study conducted in patients with epidermolysis bullosa (EB) show that regular application of the topical gel Oleogel-S10 (Filsuvez) is associated with a reduced need for daily dressing changes when compared with a control gel.

In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.

Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.

The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).

“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.

“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).

“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.

Approved in Europe, not in the United States

Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.

Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.

EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.

The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.

Dr. Kiritsi summarized the main results of the EASE trial as follows.

• Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
• Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
• Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
• Improved pain among participants aged 4 years and older while their dressings were being changed.
• Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
• Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.

The EASE study – an important trial for EB

EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.

“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.

“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.

The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.

A version of this article appeared on Medscape.com.

Additional data from the phase 3 EASE study conducted in patients with epidermolysis bullosa (EB) show that regular application of the topical gel Oleogel-S10 (Filsuvez) is associated with a reduced need for daily dressing changes when compared with a control gel.

In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.

Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.

The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).

“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.

“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).

“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.

Approved in Europe, not in the United States

Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.

Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.

EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.

The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.

Dr. Kiritsi summarized the main results of the EASE trial as follows.

• Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
• Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
• Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
• Improved pain among participants aged 4 years and older while their dressings were being changed.
• Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
• Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.

The EASE study – an important trial for EB

EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.

“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.

“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.

The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.

A version of this article appeared on Medscape.com.

Additional data from the phase 3 EASE study conducted in patients with epidermolysis bullosa (EB) show that regular application of the topical gel Oleogel-S10 (Filsuvez) is associated with a reduced need for daily dressing changes when compared with a control gel.

In a final, post hoc analysis to come from the trial, 15 of 45 (33%) patients treated with Oleogel-S10 versus 5 of 48 (10.4%) treated with the control gel were reported as no longer needing daily dressing changes at 45 days of follow-up.

Moreover, the effect was sustained, with similar percentages of patients no longer requiring daily dressing changes at 60 days (34% vs. 13%, respectively) and 90 days (36% vs. 11%) of follow-up.

The mean reduction in daily dressing changes was 1.36 for Oleogel-S10 and 0.41 for the control gel (P = .005).

“Patients who, in the beginning, had daily dressing changes had almost three fewer dressing changes every 2 weeks if they were treated with Oleogel-S10,” Dimitra Kiritsi, MD, PhD, of the department of dermatology at the University of Freiburg (Germany), reported at the annual congress of the European Academy of Dermatology and Venereology. By comparison, patients in the control group had just one fewer daily dressing change in 2 weeks.

“You might say okay, but what does this mean in terms of time?” added Dr. Kiritsi. Using historical data on the time required for whole body care (Orphanet J Rare Dis. 2020 Jan 3. doi: 10.1186/s13023-019-1279-y), it was estimated that treatment with Oleogel-S10 was associated with an overall time-saving per week of 11 hours (6.6 hours for the patient and 4.4 hours for the caregiver) and use of the control gel was associated with an overall time-saving of 4 hours (2.4 hours for the patient and 1.6 hours for the caregiver).

“This is, for our patients, important,” said Dr. Kiritsi, as “it is time that they can spend doing something nice with the family” instead, avoiding the pain and distress associated with frequent dressing changes.

Approved in Europe, not in the United States

Oleogel-S10, classified as an herbal product, contains triterpenes derived from birch bark extract, which have been formulated with sunflower oil to form a gel.

Despite being approved for use in Europe, Oleogel-S10 has not yet been approved to treat EB in the United States. The FDA did not approve Amryt Pharma’s new drug application in February 2022. The application had included data from the EASE trial.

EASE included 223 patients with dystrophic or junctional EB, including 156 children, at 58 sites in 28 countries. As such, this makes it the largest treatment study in this rare genetic disease to date.

The trial had consisted of an initial 90-day, double-blind treatment period, during which time 109 patients had used Oleogel-S10 and 114 had used a control gel. This was followed by a 24-month open-label phase, during which time all remaining patients (n = 205) had used Oleogel-S10 on top of their standard of care.

Dr. Kiritsi summarized the main results of the EASE trial as follows.

• Complete healing of target wounds (primary endpoint) in 41.3% of patients treated with Oleogel-S10 and 28.9% of patients treated with the control gel (P = .013).
• Improved total body wound burden measured by both Epidermolysis Bullosa Disease Activity and Scarring Index and Body Surface Area Percentage scores.
• Reduced frequency of dressing changes (1 less per 2 weeks for Oleogel-S10 versus 0 less per 2 weeks for control gel).
• Improved pain among participants aged 4 years and older while their dressings were being changed.
• Reduced rates of wound infection (0.9% Oleogel-S10 vs. 4.4% control gel).
• Similar rates of treatment-emergent adverse events (24.8% vs. 22.8%, respectively), which were mostly deemed to be mild or moderate.

The EASE study – an important trial for EB

EASE is an important trial for EB, the study’s principal investigator Dédée Murrell, MD, DSc, University of New South Wales, Sydney, has pointed out previously.

“This was the first EB study to meet its primary endpoint and demonstrated a statistically significant acceleration of target wound healing by day 45,” Dr. Murrell said in a press release issued by Amryt Pharma to coincide with the online publication of the trial results.

“In addition, the favorable trends we see with key secondary endpoints such as reduced wound burden, pain, and frequency of dressing changes are considered as being very meaningful for patients,” Dr. Murrell said.

The EASE study was funded by Amryt Research Limited. Dr. Kiritsi reported receiving honoraria or consultation fees from Amryt, RHEACELL GmbH, and Fibrx Derm. She also acknowledged grant or research support from DEBRA International, EB Research Partnership, Fritz-Thyssen Foundation, German Research Foundation, and RHEACELL. Dr. Murrell has ties to Amryt and Amicus and is a co-owner of the patent for topical sirolimus for EB simplex.

A version of this article appeared on Medscape.com.

A new artificial intelligence (AI) model can detect the deadliest skin cancer with 100% accuracy, highlighting the rapid improvement of AI in medicine, say researchers from the United Kingdom. AI detected more than 99% of all skin cancers.

The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.

Skin cancer is the most common cancer in the United States;  one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.

Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.

The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.

“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.

Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.

The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.

Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.

Limitations

The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.

But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.

Christopher Smith

And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.

“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”

Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”

A version of this article appeared on Medscape.com.

A new artificial intelligence (AI) model can detect the deadliest skin cancer with 100% accuracy, highlighting the rapid improvement of AI in medicine, say researchers from the United Kingdom. AI detected more than 99% of all skin cancers.

The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.

Skin cancer is the most common cancer in the United States;  one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.

Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.

The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.

“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.

Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.

The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.

Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.

Limitations

The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.

But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.

Christopher Smith

And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.

“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”

Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”

A version of this article appeared on Medscape.com.

A new artificial intelligence (AI) model can detect the deadliest skin cancer with 100% accuracy, highlighting the rapid improvement of AI in medicine, say researchers from the United Kingdom. AI detected more than 99% of all skin cancers.

The researchers tested the AI by integrating it into a clinical diagnosis process – anticipating a future in which AI helps doctors catch skin cancer faster and triage patients.

Skin cancer is the most common cancer in the United States;  one in five 5 Americans develop skin cancer by age 70. With melanoma, the deadliest skin cancer, the 5-year survival rate is better than 99% if caught early, though only about three-quarters of melanomas are caught at this stage.

Amid rising skin cancer rates come concerns that the number of dermatologists in the workforce isn’t keeping pace. That may be why the average wait time for a dermatology appointment is trending up – in 2022, it reached 34.5 days.

The study, which was presented at the European Academy of Dermatology and Venereology Congress recently and has not yet been published, involved 6,900 patients in the United Kingdom with suspected skin cancer. The patients had been referred by their primary care physicians. The researchers took images of the suspicious areas and uploaded them to the AI software. The AI’s assessment was then shared with a dermatologist.

“Note that the diagnosis issued by the AI was not hidden from the dermatologist doing the second assessment,” said lead researcher Kashini Andrew, MBBS, a dermatologist and specialist registrar at University Hospitals Birmingham NHS Foundation Trust.

Dr. Andrew acknowledged that this may have influenced the dermatologist’s opinion. But that’s the vision of how doctors could use this tool.

The AI caught 59 of 59 melanomas and 189 of 190 total skin cancers (99.5%). (The one case that the AI missed was caught by the dermatologist.) It also flagged 541 of 585 precancerous lesions (92.5%). This represented a big improvement from a 2021 version of the model, which detected 86% of melanomas, 84% of all skin cancers, and 54% of precancerous lesions.

Over the 10-month period of the study, the system saved more than 1,000 face-to-face consultations, freeing dermatologists’ time to catch more cancers and serve more patients.

Limitations

The patients in the study were from “one hospital in a single region of the UK,” and the sample was not large enough to allow broad statements to be made about the use of AI in dermatology, Dr. Andrew said.

But it can open the conversation. Roxana Daneshjou, MD, PhD, a dermatologist at Stanford (Calif.) University who has studied the pros and cons of AI in medicine, had some concerns. For one thing, doctors can gather more in-depth information during an in-person exam than AI can glean from a photo, Dr. Daneshjou noted. They can examine skin texture, gather patient history, and take photos with special lighting and magnification.

Christopher Smith

And the AI needs to get better at ruling out malignancy, Dr. Daneshjou said. In this study, the AI identified 75% of benign lesions, a decline from the earlier version. The researchers noted in the abstract that this is a potential trade-off for increased sensitivity.

“[Unnecessary] biopsies can clog up the health care system, cost money, and cause stress and scarring,” said Dr. Daneshjou. “You don’t want to increase the burden of that.”

Still, if AI software such as the kind used in the study proves just as accurate in larger, more diverse sample sizes, then it could be a powerful tool for triage, Dr. Daneshjou said. “If AI gets particularly good at finding malignancy and also ruling it out, that would be a win.”

A version of this article appeared on Medscape.com.

The antibody-drug conjugate tisotumab vedotin bested chemotherapy for the second- or third-line treatment of recurrent/metastatic cervical cancer in the InnovaTV 301 trial, which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.

Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).

Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.

Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
 

New and emerging options

The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.

TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.

Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.

Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.

The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.

In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.

It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.

One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.

Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.

Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
 

Subgroups fall short of statistical significance

In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.

The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.

In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.

Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.

The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).

The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.

The antibody-drug conjugate tisotumab vedotin bested chemotherapy for the second- or third-line treatment of recurrent/metastatic cervical cancer in the InnovaTV 301 trial, which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.

Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).

Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.

Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
 

New and emerging options

The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.

TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.

Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.

Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.

The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.

In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.

It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.

One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.

Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.

Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
 

Subgroups fall short of statistical significance

In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.

The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.

In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.

Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.

The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).

The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.

The antibody-drug conjugate tisotumab vedotin bested chemotherapy for the second- or third-line treatment of recurrent/metastatic cervical cancer in the InnovaTV 301 trial, which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.

Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).

Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.

Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
 

New and emerging options

The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.

TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.

Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.

Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.

The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.

In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.

It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.

One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.

Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.

Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
 

Subgroups fall short of statistical significance

In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.

The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.

In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.

Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.

The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).

The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.