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Selinexor on fast track for DLBCL
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of diffuse large B-cell lymphoma (DLBCL).
The designation is for selinexor to treat DLBCL patients who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or chimeric antigen receptor T-cell therapy.
Selinexor is being studied in the phase 2b SADAL trial (NCT02227251), which is enrolling patients with relapsed or refractory DLBCL who have received two to five prior therapies and are not eligible for stem cell transplant.
Top-line results from this trial are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 1677).
Selinexor is an oral selective inhibitor of nuclear export (SINE) compound being developed by Karyopharm Therapeutics Inc.
The company previously received fast track designation for selinexor to treat patients with penta-refractory multiple myeloma who have received at least three prior lines of therapy.
The FDA says its fast track program is designed to facilitate the development and expedite the review of products that are intended to treat serious conditions and have the potential to address unmet medical needs.
Fast track designation provides developers with greater access to the FDA as well as eligibility for accelerated approval, priority review, and rolling review.
“The receipt of fast track designation from the FDA for selinexor in relapsed DLBCL underscores the great unmet medical need for this aggressive form of lymphoma,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm.
“Pending positive results from the phase 2b SADAL study, we plan to submit a second NDA [new drug application] to the FDA in the first half of 2019, with a request for accelerated approval, for oral selinexor as a potential new treatment for patients with relapsed or refractory DLBCL.”
Last month, the FDA accepted a new drug application for selinexor as a treatment for penta-refractory multiple myeloma. The agency granted the application priority review and set an action date of April 6, 2019.
FDA approves elotuzumab combo for rel/ref MM
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The U.S. Food and Drug Administration (FDA) has approved elotuzumab (Empliciti®) in combination with pomalidomide and dexamethasone.
The combination is now approved for use in adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is also FDA-approved in combination with lenalidomide and dexamethasone to treat adult MM patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from the phase 2 ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June.
ELOQUENT-3 enrolled MM patients who had refractory or relapsed and refractory MM and had received both lenalidomide and a proteasome inhibitor.
The patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n=60) or pomalidomide and dexamethasone (Pd, n=57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P=0.0029). The rate of complete response or stringent complete response was 8.3% in the EPd arm and 1.8% in the Pd arm.
The median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (hazard ratio=0.54, P=0.0078).
Serious adverse events (AEs) occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious AEs (in the EPd and Pd arms, respectively) were pneumonia (13% and 11%) and respiratory tract infection (7% and 3.6%).
AEs occurring in at least 10% of patients in the EPd arm and at least 5% of those in the Pd arm (respectively) included:
- Constipation (22% and 11%)
- Hyperglycemia (20% and 15%)
- Pneumonia (18% and 13%)
- Diarrhea (18% and 9%)
- Respiratory tract infection (17% and 9%)
- Bone pain (15% and 9%)
- Dyspnea (15% and 7%)
- Muscle spasms (13% and 5%)
- Peripheral edema (13% and 7%)
- Lymphopenia (10% and 1.8%).
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available at www.empliciti.com.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Underused PV treatments save lives, doc says
Researchers have found evidence to suggest that phlebotomy and hydroxyurea (HU) provide real-world benefits for older patients with polycythemia vera (PV), but both treatments are underused.
In a study of more than 800 PV patients, phlebotomy and HU treatment were both associated with lower risks of death and thrombosis.
However, 39% of patients didn’t receive HU, and 36% didn’t undergo phlebotomy.
“Our study highlights the value of adhering to PV treatment guidelines,” said study author Nikolai A. Podoltsev, MD, PhD, of Yale Cancer Center in New Haven, Connecticut.
“Use of the two recommended treatments saves lives.”
Dr. Podoltsev and his colleagues described this survival benefit in Blood Advances.
The researchers studied data from the linked Surveillance, Epidemiology, and End Results–Medicare database. They collected information on 820 older adults diagnosed with PV from 2007 to 2013.
The patients’ median age was 77 (range, 71-83), 57% were female, 91.2% were white, 12.7% had a disability, and 13.2% had a prior thrombotic event.
Patients received the following PV treatments:
- Both phlebotomy and HU concurrently or sequentially (41.1%)
- Phlebotomy only (23.0%)
- HU only (19.6%)
- Neither phlebotomy nor HU (16.3%).
Survival
The median follow-up was 2.83 years. During that time, 37.2% of patients (n=305) died.
The median survival was 6.29 years for phlebotomy recipients and 4.50 years for non-recipients (P<0.01). The median survival was 6.02 years for HU recipients and 5.25 years for non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with decreased mortality. The hazard ratio (HR) for death was 0.65 (P<0.01) for phlebotomy recipients.
Increasing phlebotomy intensity (the number of phlebotomies per year) was also associated with decreased mortality, with an HR of 0.71 (P<0.01).
A higher proportion of days covered (PDC) by HU treatment was associated with decreased mortality as well.
The researchers said every 10% increase of HU PDC was associated with an 8% to 9% lower risk of death. The HR was 0.92 in a model where phlebotomy was a binary variable and 0.91 in a model that included the frequency of phlebotomy (P<0.01 for both).
Thrombosis
In all, 36.1% of patients (n=296) had a thrombotic event, which includes venous and arterial thrombosis.
The incidence of thrombosis was 29.3% (n=142) in phlebotomy recipients and 46.0% (n=154) in non-recipients (P<0.01). The incidence was 27.6% (n=118) in HU recipients and 45.4% (n=178) in non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with a decreased risk of thrombosis, with an HR of 0.52 (P<0.01).
Increasing phlebotomy intensity was associated with a decreased risk of thrombosis as well, with an HR of 0.46 (P<0.01).
And every 10% increase of HU PDC was associated with an 8% lower risk of thrombosis. The HR was 0.92 in both models (P<0.01 for both).
“All of the patients we studied were high-risk for clot development, and we now know from our findings that guideline-recommended treatments reduce the risk of both thrombosis and death,” Dr. Podoltsev said.
“We hope that our research will raise clinicians’ awareness of and adherence to the guidelines and improve the outcomes of PV patients in the future.”
This research was supported by the Frederick A. DeLuca Foundation. Study authors reported relationships with 24 pharmaceutical companies.
Researchers have found evidence to suggest that phlebotomy and hydroxyurea (HU) provide real-world benefits for older patients with polycythemia vera (PV), but both treatments are underused.
In a study of more than 800 PV patients, phlebotomy and HU treatment were both associated with lower risks of death and thrombosis.
However, 39% of patients didn’t receive HU, and 36% didn’t undergo phlebotomy.
“Our study highlights the value of adhering to PV treatment guidelines,” said study author Nikolai A. Podoltsev, MD, PhD, of Yale Cancer Center in New Haven, Connecticut.
“Use of the two recommended treatments saves lives.”
Dr. Podoltsev and his colleagues described this survival benefit in Blood Advances.
The researchers studied data from the linked Surveillance, Epidemiology, and End Results–Medicare database. They collected information on 820 older adults diagnosed with PV from 2007 to 2013.
The patients’ median age was 77 (range, 71-83), 57% were female, 91.2% were white, 12.7% had a disability, and 13.2% had a prior thrombotic event.
Patients received the following PV treatments:
- Both phlebotomy and HU concurrently or sequentially (41.1%)
- Phlebotomy only (23.0%)
- HU only (19.6%)
- Neither phlebotomy nor HU (16.3%).
Survival
The median follow-up was 2.83 years. During that time, 37.2% of patients (n=305) died.
The median survival was 6.29 years for phlebotomy recipients and 4.50 years for non-recipients (P<0.01). The median survival was 6.02 years for HU recipients and 5.25 years for non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with decreased mortality. The hazard ratio (HR) for death was 0.65 (P<0.01) for phlebotomy recipients.
Increasing phlebotomy intensity (the number of phlebotomies per year) was also associated with decreased mortality, with an HR of 0.71 (P<0.01).
A higher proportion of days covered (PDC) by HU treatment was associated with decreased mortality as well.
The researchers said every 10% increase of HU PDC was associated with an 8% to 9% lower risk of death. The HR was 0.92 in a model where phlebotomy was a binary variable and 0.91 in a model that included the frequency of phlebotomy (P<0.01 for both).
Thrombosis
In all, 36.1% of patients (n=296) had a thrombotic event, which includes venous and arterial thrombosis.
The incidence of thrombosis was 29.3% (n=142) in phlebotomy recipients and 46.0% (n=154) in non-recipients (P<0.01). The incidence was 27.6% (n=118) in HU recipients and 45.4% (n=178) in non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with a decreased risk of thrombosis, with an HR of 0.52 (P<0.01).
Increasing phlebotomy intensity was associated with a decreased risk of thrombosis as well, with an HR of 0.46 (P<0.01).
And every 10% increase of HU PDC was associated with an 8% lower risk of thrombosis. The HR was 0.92 in both models (P<0.01 for both).
“All of the patients we studied were high-risk for clot development, and we now know from our findings that guideline-recommended treatments reduce the risk of both thrombosis and death,” Dr. Podoltsev said.
“We hope that our research will raise clinicians’ awareness of and adherence to the guidelines and improve the outcomes of PV patients in the future.”
This research was supported by the Frederick A. DeLuca Foundation. Study authors reported relationships with 24 pharmaceutical companies.
Researchers have found evidence to suggest that phlebotomy and hydroxyurea (HU) provide real-world benefits for older patients with polycythemia vera (PV), but both treatments are underused.
In a study of more than 800 PV patients, phlebotomy and HU treatment were both associated with lower risks of death and thrombosis.
However, 39% of patients didn’t receive HU, and 36% didn’t undergo phlebotomy.
“Our study highlights the value of adhering to PV treatment guidelines,” said study author Nikolai A. Podoltsev, MD, PhD, of Yale Cancer Center in New Haven, Connecticut.
“Use of the two recommended treatments saves lives.”
Dr. Podoltsev and his colleagues described this survival benefit in Blood Advances.
The researchers studied data from the linked Surveillance, Epidemiology, and End Results–Medicare database. They collected information on 820 older adults diagnosed with PV from 2007 to 2013.
The patients’ median age was 77 (range, 71-83), 57% were female, 91.2% were white, 12.7% had a disability, and 13.2% had a prior thrombotic event.
Patients received the following PV treatments:
- Both phlebotomy and HU concurrently or sequentially (41.1%)
- Phlebotomy only (23.0%)
- HU only (19.6%)
- Neither phlebotomy nor HU (16.3%).
Survival
The median follow-up was 2.83 years. During that time, 37.2% of patients (n=305) died.
The median survival was 6.29 years for phlebotomy recipients and 4.50 years for non-recipients (P<0.01). The median survival was 6.02 years for HU recipients and 5.25 years for non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with decreased mortality. The hazard ratio (HR) for death was 0.65 (P<0.01) for phlebotomy recipients.
Increasing phlebotomy intensity (the number of phlebotomies per year) was also associated with decreased mortality, with an HR of 0.71 (P<0.01).
A higher proportion of days covered (PDC) by HU treatment was associated with decreased mortality as well.
The researchers said every 10% increase of HU PDC was associated with an 8% to 9% lower risk of death. The HR was 0.92 in a model where phlebotomy was a binary variable and 0.91 in a model that included the frequency of phlebotomy (P<0.01 for both).
Thrombosis
In all, 36.1% of patients (n=296) had a thrombotic event, which includes venous and arterial thrombosis.
The incidence of thrombosis was 29.3% (n=142) in phlebotomy recipients and 46.0% (n=154) in non-recipients (P<0.01). The incidence was 27.6% (n=118) in HU recipients and 45.4% (n=178) in non-recipients (P<0.01).
In a multivariable analysis, receipt of phlebotomy was associated with a decreased risk of thrombosis, with an HR of 0.52 (P<0.01).
Increasing phlebotomy intensity was associated with a decreased risk of thrombosis as well, with an HR of 0.46 (P<0.01).
And every 10% increase of HU PDC was associated with an 8% lower risk of thrombosis. The HR was 0.92 in both models (P<0.01 for both).
“All of the patients we studied were high-risk for clot development, and we now know from our findings that guideline-recommended treatments reduce the risk of both thrombosis and death,” Dr. Podoltsev said.
“We hope that our research will raise clinicians’ awareness of and adherence to the guidelines and improve the outcomes of PV patients in the future.”
This research was supported by the Frederick A. DeLuca Foundation. Study authors reported relationships with 24 pharmaceutical companies.
Quizartinib receives accelerated assessment for AML
The European Medicines Agency has granted accelerated assessment to the marketing authorization application (MAA) for the FLT3 inhibitor quizartinib.
With this MAA, Daiichi Sankyo Company, Ltd., is seeking authorization for quizartinib to treat adults with FLT3-ITD-positive, relapsed or refractory acute myeloid leukemia (AML).
Accelerated assessment is given to products expected to be of major interest for public health and therapeutic innovation, and it can reduce the review timeline from 210 days to 150 days.
Quizartinib also has orphan drug designation from the European Commission.
The MAA for quizartinib is based on the phase 3 QuANTUM-R study. Results from this trial were presented at the 23rd Congress of the European Hematology Association in June.
QuANTUM-R enrolled adults with FLT3-ITD AML (at least 3% FLT3-ITD allelic ratio) who had refractory disease or had relapsed within 6 months of their first complete response (CR).
Patients were randomized to receive once-daily treatment with quizartinib (n=245) or a salvage chemotherapy regimen (n=122)—low-dose cytarabine (LoDAC, n=29); combination mitoxantrone, etoposide, and cytarabine (MEC, n=40); or combination fludarabine, cytarabine, and idarubicin (FLAG-IDA, n=53).
Patients who responded to treatment could proceed to hematopoietic stem cell transplant (HSCT), and those in the quizartinib arm could resume quizartinib after HSCT.
In all, 241 patients received quizartinib, and 94 received salvage chemotherapy—LoDAC (n=22), MEC (n=25), and FLAG-IDA (n=47). Of the 28 patients in the chemotherapy group who were not treated, most withdrew consent.
Thirty-two percent of quizartinib-treated patients and 12% of the chemotherapy group went on to HSCT.
Efficacy
The median follow-up was 23.5 months. The efficacy results include all randomized patients.
The overall response rate was 69% in the quizartinib arm and 30% in the chemotherapy arm.
The composite CR rate was 48% in the quizartinib arm and 27% in the chemotherapy arm. This includes:
- The CR rate (4% and 1%, respectively)
- The rate of CR with incomplete platelet recovery (4% and 0%, respectively)
- The rate of CR with incomplete hematologic recovery (40% and 26%, respectively).
The median event-free survival was 6.0 weeks in the quizartinib arm and 3.7 weeks in the chemotherapy arm (hazard ratio=0.90, P=0.1071).
The median overall survival was 6.2 months in the quizartinib arm and 4.7 months in the chemotherapy arm (hazard ratio=0.76, P=0.0177). The 1-year overall survival rate was 27% and 20%, respectively.
Safety
The safety results include only patients who received their assigned treatment.
Grade 3 or higher hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Thrombocytopenia (35% and 34%)
- Anemia (30% and 29%)
- Neutropenia (32% and 25%)
- Febrile neutropenia (31% and 21%)
- Leukopenia (17% and 16%).
Grade 3 or higher non-hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Sepsis/septic shock (16% and 18%)
- Hypokalemia (12% and 9%)
- Pneumonia (12% and 9%)
- Fatigue (8% and 1%)
- Dyspnea (5% for both)
- Hypophosphatemia (5% for both).
The European Medicines Agency has granted accelerated assessment to the marketing authorization application (MAA) for the FLT3 inhibitor quizartinib.
With this MAA, Daiichi Sankyo Company, Ltd., is seeking authorization for quizartinib to treat adults with FLT3-ITD-positive, relapsed or refractory acute myeloid leukemia (AML).
Accelerated assessment is given to products expected to be of major interest for public health and therapeutic innovation, and it can reduce the review timeline from 210 days to 150 days.
Quizartinib also has orphan drug designation from the European Commission.
The MAA for quizartinib is based on the phase 3 QuANTUM-R study. Results from this trial were presented at the 23rd Congress of the European Hematology Association in June.
QuANTUM-R enrolled adults with FLT3-ITD AML (at least 3% FLT3-ITD allelic ratio) who had refractory disease or had relapsed within 6 months of their first complete response (CR).
Patients were randomized to receive once-daily treatment with quizartinib (n=245) or a salvage chemotherapy regimen (n=122)—low-dose cytarabine (LoDAC, n=29); combination mitoxantrone, etoposide, and cytarabine (MEC, n=40); or combination fludarabine, cytarabine, and idarubicin (FLAG-IDA, n=53).
Patients who responded to treatment could proceed to hematopoietic stem cell transplant (HSCT), and those in the quizartinib arm could resume quizartinib after HSCT.
In all, 241 patients received quizartinib, and 94 received salvage chemotherapy—LoDAC (n=22), MEC (n=25), and FLAG-IDA (n=47). Of the 28 patients in the chemotherapy group who were not treated, most withdrew consent.
Thirty-two percent of quizartinib-treated patients and 12% of the chemotherapy group went on to HSCT.
Efficacy
The median follow-up was 23.5 months. The efficacy results include all randomized patients.
The overall response rate was 69% in the quizartinib arm and 30% in the chemotherapy arm.
The composite CR rate was 48% in the quizartinib arm and 27% in the chemotherapy arm. This includes:
- The CR rate (4% and 1%, respectively)
- The rate of CR with incomplete platelet recovery (4% and 0%, respectively)
- The rate of CR with incomplete hematologic recovery (40% and 26%, respectively).
The median event-free survival was 6.0 weeks in the quizartinib arm and 3.7 weeks in the chemotherapy arm (hazard ratio=0.90, P=0.1071).
The median overall survival was 6.2 months in the quizartinib arm and 4.7 months in the chemotherapy arm (hazard ratio=0.76, P=0.0177). The 1-year overall survival rate was 27% and 20%, respectively.
Safety
The safety results include only patients who received their assigned treatment.
Grade 3 or higher hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Thrombocytopenia (35% and 34%)
- Anemia (30% and 29%)
- Neutropenia (32% and 25%)
- Febrile neutropenia (31% and 21%)
- Leukopenia (17% and 16%).
Grade 3 or higher non-hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Sepsis/septic shock (16% and 18%)
- Hypokalemia (12% and 9%)
- Pneumonia (12% and 9%)
- Fatigue (8% and 1%)
- Dyspnea (5% for both)
- Hypophosphatemia (5% for both).
The European Medicines Agency has granted accelerated assessment to the marketing authorization application (MAA) for the FLT3 inhibitor quizartinib.
With this MAA, Daiichi Sankyo Company, Ltd., is seeking authorization for quizartinib to treat adults with FLT3-ITD-positive, relapsed or refractory acute myeloid leukemia (AML).
Accelerated assessment is given to products expected to be of major interest for public health and therapeutic innovation, and it can reduce the review timeline from 210 days to 150 days.
Quizartinib also has orphan drug designation from the European Commission.
The MAA for quizartinib is based on the phase 3 QuANTUM-R study. Results from this trial were presented at the 23rd Congress of the European Hematology Association in June.
QuANTUM-R enrolled adults with FLT3-ITD AML (at least 3% FLT3-ITD allelic ratio) who had refractory disease or had relapsed within 6 months of their first complete response (CR).
Patients were randomized to receive once-daily treatment with quizartinib (n=245) or a salvage chemotherapy regimen (n=122)—low-dose cytarabine (LoDAC, n=29); combination mitoxantrone, etoposide, and cytarabine (MEC, n=40); or combination fludarabine, cytarabine, and idarubicin (FLAG-IDA, n=53).
Patients who responded to treatment could proceed to hematopoietic stem cell transplant (HSCT), and those in the quizartinib arm could resume quizartinib after HSCT.
In all, 241 patients received quizartinib, and 94 received salvage chemotherapy—LoDAC (n=22), MEC (n=25), and FLAG-IDA (n=47). Of the 28 patients in the chemotherapy group who were not treated, most withdrew consent.
Thirty-two percent of quizartinib-treated patients and 12% of the chemotherapy group went on to HSCT.
Efficacy
The median follow-up was 23.5 months. The efficacy results include all randomized patients.
The overall response rate was 69% in the quizartinib arm and 30% in the chemotherapy arm.
The composite CR rate was 48% in the quizartinib arm and 27% in the chemotherapy arm. This includes:
- The CR rate (4% and 1%, respectively)
- The rate of CR with incomplete platelet recovery (4% and 0%, respectively)
- The rate of CR with incomplete hematologic recovery (40% and 26%, respectively).
The median event-free survival was 6.0 weeks in the quizartinib arm and 3.7 weeks in the chemotherapy arm (hazard ratio=0.90, P=0.1071).
The median overall survival was 6.2 months in the quizartinib arm and 4.7 months in the chemotherapy arm (hazard ratio=0.76, P=0.0177). The 1-year overall survival rate was 27% and 20%, respectively.
Safety
The safety results include only patients who received their assigned treatment.
Grade 3 or higher hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Thrombocytopenia (35% and 34%)
- Anemia (30% and 29%)
- Neutropenia (32% and 25%)
- Febrile neutropenia (31% and 21%)
- Leukopenia (17% and 16%).
Grade 3 or higher non-hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Sepsis/septic shock (16% and 18%)
- Hypokalemia (12% and 9%)
- Pneumonia (12% and 9%)
- Fatigue (8% and 1%)
- Dyspnea (5% for both)
- Hypophosphatemia (5% for both).
Combo appears safe, active in rel/ref NHL
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
Changes related to AML relapse may be reversible
New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.
Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.
However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.
Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.
The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.
The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.
Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.
Findings
The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.
The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.
They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.
The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.
RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.
Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.
The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.
To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.
Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”
This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.
Several study authors reported personal fees and/or research support from industry outside the submitted work.
New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.
Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.
However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.
Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.
The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.
The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.
Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.
Findings
The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.
The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.
They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.
The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.
RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.
Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.
The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.
To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.
Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”
This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.
Several study authors reported personal fees and/or research support from industry outside the submitted work.
New research suggests relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT) is related to changes in immune-related gene expression that may be reversible.
Researchers observed downregulation of major histocompatibility complex (MHC) class II genes in samples from patients who relapsed after HSCT.
However, interferon-gamma “rapidly reversed this phenotype” in vitro, according to the researchers.
Matthew J. Christopher, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported these findings in The New England Journal of Medicine.
The researchers set out to determine how genetic and epigenetic changes after HSCT may allow leukemic cells to avoid the graft-vs-leukemia effect and to see whether immune-related genes are affected by HSCT.
The team analyzed paired samples obtained at diagnosis and relapse from 15 AML patients who relapsed after HSCT and 20 AML patients who relapsed after chemotherapy. The team also analyzed additional samples from patients who relapsed after HSCT to validate initial findings.
Methods of analysis included enhanced exome sequencing, RNA sequencing, flow cytometry, and immunohistochemical analysis.
Findings
The researchers first looked for relapse-specific mutations but found no driver mutations associated with relapse after HSCT.
The mutations seen post-HSCT relapse were generally similar to those seen both before treatment and after relapse in patients who had undergone chemotherapy, and the researchers could not identify any patterns of mutations related to relapse.
They then looked for, but did not find, relapse-specific mutations in genes involved in modulation of immune checkpoints, antigen presentation, or cytokine signaling.
The researchers did, however, find evidence of epigenetic changes that were more common in the samples from patients with post-transplant relapses.
RNA sequencing showed that MHC class II genes (HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) were downregulated three- to 12-fold after transplant.
Flow cytometry and immunohistochemical analysis confirmed that MHC class II expression was decreased at relapse after HSCT in 17 of 34 samples evaluated.
The researchers said there was no association between the downregulation of MHC class II and donor type or use of immunosuppression.
To see whether the downregulation of MHC class II genes was reversible, the researchers treated three post-HSCT relapse samples with interferon-gamma, which is known to upregulate MHC class II on certain cells.
Culturing patient cells with interferon-gamma “rapidly induced MHC class II protein expression on leukemic blasts,” the researchers said. They observed “essentially full restoration of MHC class II protein expression in nearly all AML blasts after 72 hours.”
This study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and the Barnes-Jewish Hospital Foundation.
Several study authors reported personal fees and/or research support from industry outside the submitted work.
Sandoz won’t seek U.S. approval for rituximab biosimilar
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
Sandoz has decided not to pursue U.S. approval for its rituximab product (GP2013), a proposed biosimiliar of Rituxan/Mabthera.
GP2013 (Rixathon, Riximyo) is already approved outside the U.S.
Sandoz was seeking U.S. approval of GP2013 for all the same indications as the reference product—B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.
The U.S. Food and Drug Administration (FDA) had accepted the biologics license application (BLA) for GP2013 in September 2017.
In May of this year, the FDA issued a complete response letter saying it could not approve GP2013. The agency also requested additional information to complement the BLA submission for GP2013.
At the time of the complete response letter, Sandoz said it was still committed to bringing GP2013 to the U.S. market. Now, the company’s position has changed.
“We appreciate the important conversations with the FDA, which have provided specific requirements for our potential U.S. biosimilar rituximab, but believe the patient and marketplace needs in the U.S. will be satisfied before we can generate the data required,” said Stefan Hendriks, global head of biopharmaceuticals at Sandoz.
“We are disappointed to have to make this decision and stand behind the safety, efficacy, and quality of our medicine, which met the stringent criteria for approval in the European Union, Switzerland, Japan, New Zealand, and Australia.”
The BLA for GP2013 was supported, in part, by the ASSIST-FL trial (NCT01419665), in which researchers compared GP2013 to the reference product. Results from this trial were published in The Lancet Haematology in July 2017.
The phase 3 trial included adults with previously untreated, advanced stage follicular lymphoma. Patients received 8 cycles of cyclophosphamide, vincristine, and prednisone with either GP2013 or reference rituximab. Responders then received GP2013 or rituximab monotherapy as maintenance for up to 2 years.
At a median follow-up of 11.6 months, the overall response rate was 87% (271/311) in the GP2013 arm and 88% in the rituximab arm (274/313). Complete response rates were 15% (n=46) and 13% (n=42), respectively.
Rates of adverse events (AEs) were 93% in the GP2013 arm and 91% in the rituximab arm. Rates of serious AEs were 23% and 20%, respectively. The rate of discontinuation due to AEs was 7% in both arms.
The most common AE was neutropenia, which occurred in 26% of patients in the GP2013 arm and 30% of those in the rituximab arm in the combination phase. Rates of neutropenia in the maintenance phase were 10% and 6%, respectively.
CPI-0610 receives fast track designation for MF
The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).
CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.
The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.
The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).
In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:
- Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
- MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
- MF patients who are anemic and have not previously received a JAK inhibitor.
According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.
The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).
One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.
The company said proof-of-concept data from this trial are expected in mid-2019.
About fast track designation
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).
CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.
The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.
The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).
In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:
- Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
- MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
- MF patients who are anemic and have not previously received a JAK inhibitor.
According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.
The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).
One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.
The company said proof-of-concept data from this trial are expected in mid-2019.
About fast track designation
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to CPI-0610 for the treatment of myelofibrosis (MF).
CPI-0610 is a BET inhibitor being developed by Constellation Pharmaceuticals, Inc.
The company said results from preclinical studies and translational insights from the first-in-human study of CPI-0610 led to the prioritization of CPI-0610 as a potential treatment for MF.
The company is now enrolling patients in the phase 2 portion of the phase 1/2 MANIFEST trial (NCT02158858).
In this trial, researchers are testing CPI-0610 alone or in combination with ruxolitinib in the following patient groups:
- Transfusion-dependent or -independent MF patients who have previously received a JAK inhibitor and are ineligible for or cannot tolerate additional JAK inhibitor therapy, lost response to a JAK inhibitor, or are resistant or refractory to JAK inhibition
- MF patients who are transfusion-dependent or -independent whose disease is not being adequately controlled by ruxolitinib
- MF patients who are anemic and have not previously received a JAK inhibitor.
According to Constellation Pharmaceuticals, CPI-0610 demonstrated clinical activity in the first four patients treated on this trial, all of whom previously received a JAK inhibitor.
The researchers observed reductions in spleen volume and improvements in hemoglobin levels in patients who received monotherapy (n=2) or CPI-0610 plus ruxolitinib (n=2).
One patient treated with the combination experienced resolution of thrombocytosis and became transfusion-independent.
The company said proof-of-concept data from this trial are expected in mid-2019.
About fast track designation
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
Denosumab fights osteoporosis in TDT patients
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.
Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.
They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms.
However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).
And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).
Results
The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.
At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).
The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).
And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).
However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:
- Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
- Osteoprotegerin (OPG)
- sRANKL/OPG ratio
- C-terminal crosslinking telopeptide of type I collagen (CTX)
- TRACP-5b
- bALP.
There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.
In all, there were 17 adverse events (AEs) in 14 patients.
There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.
There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.
This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.
Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.
They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms.
However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).
And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).
Results
The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.
At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).
The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).
And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).
However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:
- Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
- Osteoprotegerin (OPG)
- sRANKL/OPG ratio
- C-terminal crosslinking telopeptide of type I collagen (CTX)
- TRACP-5b
- bALP.
There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.
In all, there were 17 adverse events (AEs) in 14 patients.
There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.
There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.
This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.
Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.
They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms.
However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).
And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).
Results
The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.
At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).
The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).
And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).
However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:
- Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
- Osteoprotegerin (OPG)
- sRANKL/OPG ratio
- C-terminal crosslinking telopeptide of type I collagen (CTX)
- TRACP-5b
- bALP.
There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.
In all, there were 17 adverse events (AEs) in 14 patients.
There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.
There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.
This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.
FDA and EC approve pegfilgrastim biosimilar
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”
The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).
Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.
Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”
The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”
The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.
The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).
Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.
“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.
“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”