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Myeloma: First-In-Class ADC Regimen Yields Key Benefits
“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.
The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).
The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).
The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.
The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.
While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.
Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.
In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.
Discontinuation rates for fatal or AEs of any cause were similar in both arms.
The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).
The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.
As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.
The AEs resulted in treatment discontinuation for 9% of patients.
The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.
“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.
Previous FDA Approval Withdrawn
Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).
However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.
Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”
While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”
Antibody-Drug Conjugates: Less is More?
The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”
In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).
In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”
He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”
“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.
“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.
That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”
And “less ocular toxicity with similar efficacy are big wins,” he added.
“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”
Other Therapies
In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.
Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.
While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.
“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.
The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.
The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.
“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.
The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).
The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).
The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.
The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.
While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.
Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.
In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.
Discontinuation rates for fatal or AEs of any cause were similar in both arms.
The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).
The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.
As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.
The AEs resulted in treatment discontinuation for 9% of patients.
The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.
“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.
Previous FDA Approval Withdrawn
Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).
However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.
Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”
While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”
Antibody-Drug Conjugates: Less is More?
The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”
In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).
In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”
He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”
“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.
“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.
That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”
And “less ocular toxicity with similar efficacy are big wins,” he added.
“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”
Other Therapies
In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.
Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.
While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.
“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.
The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.
The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.
“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.
The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).
The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).
The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.
The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.
While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.
Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.
In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.
Discontinuation rates for fatal or AEs of any cause were similar in both arms.
The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).
The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.
As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.
The AEs resulted in treatment discontinuation for 9% of patients.
The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.
“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.
Previous FDA Approval Withdrawn
Of note, belantamab mafodotin previously generated high interest for relapsed/refractory multiple melanoma, with early clinical results earning the therapy accelerated approval from the US Food and Drug Administration (FDA).
However, the FDA approval was subsequently revoked when the DREAMM-3 trial filed to achieve its primary outcome of superior PFS.
Dr. Trudel explained in an interview that since then, key changes have included combinations to improve responses, “overcome early progression and allow patients to benefit from the long duration of response that is achieved with belantamab mafodotin once they respond.”
While the ocular toxicities are common, Dr. Trudel underscored that they are “reversible and manageable.”
Antibody-Drug Conjugates: Less is More?
The ocular AEs observed with belantamab mafodotin are among the variety of unique side effects that are reported with the emerging antibody-drug conjugates, which, with precision targeting, deliver highly potent cytotoxic ‘payloads’ that bind to cells, earning the drugs nicknames such as “smart bombs” and “biologic missiles.”
In the case of belantamab mafodotin, the target is the protein B-cell maturation antigen (BCMA).
In a commentary on the DREAMM-8 study presented at the meeting, Sagar Lonial, MD, chair of the department of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, noted the importance of BCMA: “In describing it to fellows, I explain that everything bad that a myeloma cell wants to do is mediated through BCMA.”
He underscored, however, the need to consider strategic dosing reductions, evoking iconic architect Ludwig Mies van der Rohe’s adage “less is more.”
“These results show belantamab mafodotin is clearly effective, but the question is how do we most effectively deliver it,” he said. “The idea that more is better is not necessarily the case when we’re talking about antibody drug conjugates,” he said.
“We need to use less [drug], less frequently, and do it in a way that preserves patient function,” Dr. Lonial said. “Missed doses may actually result in better safety profiles and maintain the efficacy of the treatment,” he said.
That being said, Dr. Lonial emphasized that the DREAMM-8 study is important, showing “the longest PFS in a pom-dex combination that we’ve seen in multiple myeloma.”
And “less ocular toxicity with similar efficacy are big wins,” he added.
“Future studies should take less frequent dosing into account as they are planned and as they’re executed.”
Other Therapies
In addition to the bortezomib, pom-dex regimen, other currently approved triplet regimens used at the first relapse in multiple myeloma include selinexor-bortezomib-dexamethasone, however that regimen is associated with adverse events that can pose challenges.
Furthermore, two chimeric antigen receptor (CAR) T-cell therapies — ciltacabtagene autoleucel and idecabtagene vicleucel, have emerged and been approved for multiple myeloma patients who have received at least one and at least two previous lines of therapy, respectively.
While those CAR T-cell therapies show important improvements in PFS benefit and quality of life compared with standard triplet regimens, access is a significant stumbling block, and safety issues, including the potential for cytokine release syndrome and neurotoxic effects are also a concern.
“Each regimen for myeloma comes with unique toxicities. Thus, it is beneficial for physicians and patients to have access to multiple treatment regimens to individualize to the patient, based on patient characteristics [and] drug related factors,” Dr. Trudel said.
The current DREAMM-8 regimen represents a convenient, “off-the-shelf option that can be given in the community,” she added.
The trial was sponsored by GSK. Dr. Trudel disclosed relationships with Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Jansen Biotech, Pfizer, Roche, and Sanofi. Dr. Lonial reported ties with Takeda, Amgen, Novartis, BMS, GSK, ABBVIE, Genentech, Pfizer, Regeneron, Janssen, and TG Therapeutics.
FROM ASCO 2024
Would Making Tuition Free Address the Primary Care Shortage?
This transcript has been edited for clarity.
Would free medical school encourage more students to pursue primary care? Overpriced medical training in this country definitely contributes to burnout and the physician shortage, and all that debt may influence what type of specialty somebody goes into.
Assumptions Behind Free Tuition Initiatives
Now, this question is based on an assumption that there already is a large group of medical students who want to go into primary care, and the reason they’re not or the reason they’re reluctant to is because of tuition. If you take that stress away, you fix the problem.
This was at least part of the assumption made when NYU announced free tuition for all medical students back in 2018. One goal was to encourage more students to go into primary care. The other was to broaden the application pool to include more diverse students from different socioeconomic and racial backgrounds. We›ll get back to that.
Quick numbers. In NYU’s 2022 match, the first tuition-free class, about 25% of students matched into a primary care specialty— internal medicine or pediatrics — and there were zero matches into a family medicine residency. I can’t find the data, but anecdotally that 25% is a slight increase from prior years.
Primary Care Match Rates Post–Tuition Waiver
There’s some fine print to consider. Some of the residents who matched into internal medicine or pediatric programs may subspecialize and not work in outpatient medicine at all. Also, a majority of students matched in major urban areas such as New York, Boston, or Los Angeles. We know that historically, people tend to work where they train, so that’s not looking too great for recruitment to rural communities or underserved areas.
There is some hope. In 2024, slightly more students from NYU matched into primary care specialties, including to family medicine. This is amidst a new record in family med residency matches nationwide. Rightfully, in the beginning, NYU was applauded for this tuition-free decision, but there was some criticism about who should be prioritized for financial assistance. Consider a future surgeon from a wealthy family vs a first-generation student committed to rural primary care.
NYU said, “No, equality for all.” Even acclaimed physician and bioethicist, Dr Ezekiel Emanuel weighed in and suggested “forgiving medical school debt for students who commit to a career in primary care in an underserved area. Two years of service for each year of free tuition.” At least this would allow resources to be focused only on building a primary care pool.
Also, after the tuition-free announcement, applications to NYU increased by almost 50%, and from underrepresented groups, 100%. Not that surprising. The average MCAT score and GPA also increased, but the acceptance rate stayed at around 2%.
How much difference will this tuition-free program really make in the future? Time will tell, but I do think that NYU set an important precedent here. Medical schools should be critically looking at where tuition money goes and what financial incentives could be used to attract a more diverse student body, with more hopefully going into primary care.
Let’s take a look at NYU’s Grossman Long Island campus. They have an accelerated 3-year program, tuition-free, primary care focused, and 67% of their graduates went into primary care.
In California, Kaiser Permanente School of Medicine, which is also tuition-free and focused, had 38% of their graduates go to primary care.
What are these programs doing differently? Well, they’re tuition-free, they have focused tracks, and they have enough accredited sites so that students can get a realistic and broad look of what it’s actually like to practice primary care.
Attracting Med Students to Primary Care
This leads to a broader question: How do we create an environment beyond tuition that encourages more students to go into internal medicine, pediatrics, or family medicine?
Right now, across those three specialties, the average salary is $250,000, which is lower than in other subspecialties. There’s a high amount of administrative workload, loss of autonomy, and plenty of burnout. You want to get more students to go into primary care? We need to fix primary care.
That involves many factors. Get ready for this. I actually had to make a list based on what I’ve read in articles and heard from my colleagues.
If we want to attract more students to primary care, we need to talk about:
- Improving reimbursement;
- Better mental health support;
- Highlighting the importance primary care plays in public health;
- Expanding care teams;
- Creating more medical students and training sites in rural and underserved areas;
- Expanding the use of telehealth services;
- Creating early exposure programs for high school and college students; and
- Paying attention to how local policies and statistics, such as crime, housing, and abortion bans, may push people away from practicing in certain areas or states.
Clearly, this is a large number of considerations that goes far beyond the altruistic tuition-free gifts.
Look, it’s no surprise we have a physician shortage that affects multiple specialties, but it is alarming that by 2034, there’s going to be an estimated shortage of 50,000 primary care doctors.
Stay Tuned
What do you all think? Is free tuition enough to actually move the needle in the long term, or should NYU have made a more focused gift? Comment below.
I know what you’re all wondering why I didn’t talk about tuition waivers in terms of diversifying the student body. That’s because that deserves its own video. Stay tuned for part 2.
Dr. Patel is a pediatric hospitalist, television producer, media contributor, and digital health enthusiast. He splits his time between New York City and San Francisco, as he is on faculty at Columbia University/Morgan Stanley Children’s Hospital and UCSF Benioff Children’s Hospital. He hosts The Hospitalist Retort video blog on Medscape.
Dr. Patel has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Medumo Inc.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Would free medical school encourage more students to pursue primary care? Overpriced medical training in this country definitely contributes to burnout and the physician shortage, and all that debt may influence what type of specialty somebody goes into.
Assumptions Behind Free Tuition Initiatives
Now, this question is based on an assumption that there already is a large group of medical students who want to go into primary care, and the reason they’re not or the reason they’re reluctant to is because of tuition. If you take that stress away, you fix the problem.
This was at least part of the assumption made when NYU announced free tuition for all medical students back in 2018. One goal was to encourage more students to go into primary care. The other was to broaden the application pool to include more diverse students from different socioeconomic and racial backgrounds. We›ll get back to that.
Quick numbers. In NYU’s 2022 match, the first tuition-free class, about 25% of students matched into a primary care specialty— internal medicine or pediatrics — and there were zero matches into a family medicine residency. I can’t find the data, but anecdotally that 25% is a slight increase from prior years.
Primary Care Match Rates Post–Tuition Waiver
There’s some fine print to consider. Some of the residents who matched into internal medicine or pediatric programs may subspecialize and not work in outpatient medicine at all. Also, a majority of students matched in major urban areas such as New York, Boston, or Los Angeles. We know that historically, people tend to work where they train, so that’s not looking too great for recruitment to rural communities or underserved areas.
There is some hope. In 2024, slightly more students from NYU matched into primary care specialties, including to family medicine. This is amidst a new record in family med residency matches nationwide. Rightfully, in the beginning, NYU was applauded for this tuition-free decision, but there was some criticism about who should be prioritized for financial assistance. Consider a future surgeon from a wealthy family vs a first-generation student committed to rural primary care.
NYU said, “No, equality for all.” Even acclaimed physician and bioethicist, Dr Ezekiel Emanuel weighed in and suggested “forgiving medical school debt for students who commit to a career in primary care in an underserved area. Two years of service for each year of free tuition.” At least this would allow resources to be focused only on building a primary care pool.
Also, after the tuition-free announcement, applications to NYU increased by almost 50%, and from underrepresented groups, 100%. Not that surprising. The average MCAT score and GPA also increased, but the acceptance rate stayed at around 2%.
How much difference will this tuition-free program really make in the future? Time will tell, but I do think that NYU set an important precedent here. Medical schools should be critically looking at where tuition money goes and what financial incentives could be used to attract a more diverse student body, with more hopefully going into primary care.
Let’s take a look at NYU’s Grossman Long Island campus. They have an accelerated 3-year program, tuition-free, primary care focused, and 67% of their graduates went into primary care.
In California, Kaiser Permanente School of Medicine, which is also tuition-free and focused, had 38% of their graduates go to primary care.
What are these programs doing differently? Well, they’re tuition-free, they have focused tracks, and they have enough accredited sites so that students can get a realistic and broad look of what it’s actually like to practice primary care.
Attracting Med Students to Primary Care
This leads to a broader question: How do we create an environment beyond tuition that encourages more students to go into internal medicine, pediatrics, or family medicine?
Right now, across those three specialties, the average salary is $250,000, which is lower than in other subspecialties. There’s a high amount of administrative workload, loss of autonomy, and plenty of burnout. You want to get more students to go into primary care? We need to fix primary care.
That involves many factors. Get ready for this. I actually had to make a list based on what I’ve read in articles and heard from my colleagues.
If we want to attract more students to primary care, we need to talk about:
- Improving reimbursement;
- Better mental health support;
- Highlighting the importance primary care plays in public health;
- Expanding care teams;
- Creating more medical students and training sites in rural and underserved areas;
- Expanding the use of telehealth services;
- Creating early exposure programs for high school and college students; and
- Paying attention to how local policies and statistics, such as crime, housing, and abortion bans, may push people away from practicing in certain areas or states.
Clearly, this is a large number of considerations that goes far beyond the altruistic tuition-free gifts.
Look, it’s no surprise we have a physician shortage that affects multiple specialties, but it is alarming that by 2034, there’s going to be an estimated shortage of 50,000 primary care doctors.
Stay Tuned
What do you all think? Is free tuition enough to actually move the needle in the long term, or should NYU have made a more focused gift? Comment below.
I know what you’re all wondering why I didn’t talk about tuition waivers in terms of diversifying the student body. That’s because that deserves its own video. Stay tuned for part 2.
Dr. Patel is a pediatric hospitalist, television producer, media contributor, and digital health enthusiast. He splits his time between New York City and San Francisco, as he is on faculty at Columbia University/Morgan Stanley Children’s Hospital and UCSF Benioff Children’s Hospital. He hosts The Hospitalist Retort video blog on Medscape.
Dr. Patel has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Medumo Inc.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Would free medical school encourage more students to pursue primary care? Overpriced medical training in this country definitely contributes to burnout and the physician shortage, and all that debt may influence what type of specialty somebody goes into.
Assumptions Behind Free Tuition Initiatives
Now, this question is based on an assumption that there already is a large group of medical students who want to go into primary care, and the reason they’re not or the reason they’re reluctant to is because of tuition. If you take that stress away, you fix the problem.
This was at least part of the assumption made when NYU announced free tuition for all medical students back in 2018. One goal was to encourage more students to go into primary care. The other was to broaden the application pool to include more diverse students from different socioeconomic and racial backgrounds. We›ll get back to that.
Quick numbers. In NYU’s 2022 match, the first tuition-free class, about 25% of students matched into a primary care specialty— internal medicine or pediatrics — and there were zero matches into a family medicine residency. I can’t find the data, but anecdotally that 25% is a slight increase from prior years.
Primary Care Match Rates Post–Tuition Waiver
There’s some fine print to consider. Some of the residents who matched into internal medicine or pediatric programs may subspecialize and not work in outpatient medicine at all. Also, a majority of students matched in major urban areas such as New York, Boston, or Los Angeles. We know that historically, people tend to work where they train, so that’s not looking too great for recruitment to rural communities or underserved areas.
There is some hope. In 2024, slightly more students from NYU matched into primary care specialties, including to family medicine. This is amidst a new record in family med residency matches nationwide. Rightfully, in the beginning, NYU was applauded for this tuition-free decision, but there was some criticism about who should be prioritized for financial assistance. Consider a future surgeon from a wealthy family vs a first-generation student committed to rural primary care.
NYU said, “No, equality for all.” Even acclaimed physician and bioethicist, Dr Ezekiel Emanuel weighed in and suggested “forgiving medical school debt for students who commit to a career in primary care in an underserved area. Two years of service for each year of free tuition.” At least this would allow resources to be focused only on building a primary care pool.
Also, after the tuition-free announcement, applications to NYU increased by almost 50%, and from underrepresented groups, 100%. Not that surprising. The average MCAT score and GPA also increased, but the acceptance rate stayed at around 2%.
How much difference will this tuition-free program really make in the future? Time will tell, but I do think that NYU set an important precedent here. Medical schools should be critically looking at where tuition money goes and what financial incentives could be used to attract a more diverse student body, with more hopefully going into primary care.
Let’s take a look at NYU’s Grossman Long Island campus. They have an accelerated 3-year program, tuition-free, primary care focused, and 67% of their graduates went into primary care.
In California, Kaiser Permanente School of Medicine, which is also tuition-free and focused, had 38% of their graduates go to primary care.
What are these programs doing differently? Well, they’re tuition-free, they have focused tracks, and they have enough accredited sites so that students can get a realistic and broad look of what it’s actually like to practice primary care.
Attracting Med Students to Primary Care
This leads to a broader question: How do we create an environment beyond tuition that encourages more students to go into internal medicine, pediatrics, or family medicine?
Right now, across those three specialties, the average salary is $250,000, which is lower than in other subspecialties. There’s a high amount of administrative workload, loss of autonomy, and plenty of burnout. You want to get more students to go into primary care? We need to fix primary care.
That involves many factors. Get ready for this. I actually had to make a list based on what I’ve read in articles and heard from my colleagues.
If we want to attract more students to primary care, we need to talk about:
- Improving reimbursement;
- Better mental health support;
- Highlighting the importance primary care plays in public health;
- Expanding care teams;
- Creating more medical students and training sites in rural and underserved areas;
- Expanding the use of telehealth services;
- Creating early exposure programs for high school and college students; and
- Paying attention to how local policies and statistics, such as crime, housing, and abortion bans, may push people away from practicing in certain areas or states.
Clearly, this is a large number of considerations that goes far beyond the altruistic tuition-free gifts.
Look, it’s no surprise we have a physician shortage that affects multiple specialties, but it is alarming that by 2034, there’s going to be an estimated shortage of 50,000 primary care doctors.
Stay Tuned
What do you all think? Is free tuition enough to actually move the needle in the long term, or should NYU have made a more focused gift? Comment below.
I know what you’re all wondering why I didn’t talk about tuition waivers in terms of diversifying the student body. That’s because that deserves its own video. Stay tuned for part 2.
Dr. Patel is a pediatric hospitalist, television producer, media contributor, and digital health enthusiast. He splits his time between New York City and San Francisco, as he is on faculty at Columbia University/Morgan Stanley Children’s Hospital and UCSF Benioff Children’s Hospital. He hosts The Hospitalist Retort video blog on Medscape.
Dr. Patel has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Medumo Inc.
A version of this article appeared on Medscape.com.
Why Are We Undertreating So Many Pulmonary Embolisms?
LONG BEACH, CALIFORNIA — A small fraction of patients with pulmonary embolism (PE) who are eligible for advanced therapies are actually getting them, reported investigators who conducted a big data analysis.
“Advanced PE therapy seems to be vulnerable to disparate use, and perhaps underuse,” Sahil Parikh, MD, a cardiovascular interventionalist at the Columbia University Medical Center in New York, said when he presented results from the REAL-PE study at the Society for Cardiovascular Angiography and Interventions (SCAI) 2024 Scientific Sessions.
The underuse of advanced PE therapies is “the controversy,” Dr. Parikh said after his presentation. “It remains unclear what the role of invasive therapy is in the management of so-called high-intermediate–risk people. There isn’t a Class 1 guideline recommendation, and there is a very rapidly evolving trend that we’re increasingly treating these patients invasively,” he said.
“However, if you come to these meetings [such as SCAI], you might think everyone is getting one of these devices, but these data show that’s not the case,” Dr. Parikh said.
The analysis mined deidentified data from Truveta, a collective of health systems that provides regulatory-grade electronic health record data for research.
The researchers accessed data on patients treated with ultrasound-assisted catheter-directed thrombolysis or mechanical thrombectomy, identified from claims codes. Patient characteristics — age, race, ethnicity, sex, comorbidities, and diagnoses — were also accessed for the analysis. Earlier results were published in the January issue of the Journal of the Society for Cardiovascular Angioplasty Interventions.
Less Intervention for Black Patients and Women
White patients were more likely to receive advanced therapy than were Black patients (0.5% vs 0.37%; P = .000), Dr. Parikh reported, and women were less likely to receive advanced therapy than were men (0.41% vs 0.55%; P = .000).
The only discernable differences in outcomes were in major bleeding events in the 7 days after the procedure, which affected more White patients than it did Black patients (13.9% vs 9.3%) and affected more women than it did men (16.6% vs 11.1%).
What’s noteworthy about this study is that it demonstrates the potential of advanced data analytics to identify disparities in care and outcomes, Dr. Parikh said during his presentation. “These analyses provide a means of evaluating disparities in real clinical practice, both in the area of PE and otherwise, and may also be used for real-time monitoring of clinical decision-making and decisional support,” he said. “We do think that both novel and established therapies can benefit equally from similar types of analyses.”
Big Data Signaling Disparities
“That’s where these data are helpful,” Dr. Parikh explained. They provide “a real snapshot of how many procedures are being performed and in what kinds of patients. The low number of patients getting the procedure would suggest that there are probably more patients who would be eligible for treatment based on some of the emerging consensus documents, and they’re not receiving them.”
The data are “hypotheses generating,” Dr. Parikh said in an interview. “These hypotheses have to be evaluated further in more granular databases.”
REAL-PE is also a “clarion call” for clinical trials of investigative devices going forward, he said. “In those trials, we need to endeavor to enroll enough women and men, minority and nonminority patients so that we can make meaningful assessments of differences in efficacy and safety.”
This study is “real proof that big data can be used to provide information on outcomes for patients in a very rapid manner; that’s really exciting,” said Ethan Korngold, MD, chair of structural and interventional cardiology at the Providence Health Institute in Portland, Oregon. “This is an area of great research with great innovation, and it’s proof that, with these type of techniques using artificial intelligence and big data, we can generate data quickly on how we’re doing and what kind of patients we’re reaching.”
Findings like these may also help identify sources of the disparities, Dr. Korngold added.
“This shows we need to be reaching every patient with advanced therapies,” he said. “Different hospitals have different capabilities and different expertise in this area and they reach different patient populations. A lot of the difference in utilization stems from this fact,” he said.
“It just underscores the fact that we need to standardize our treatment approaches, and then we need to reach every person who’s suffering from this disease,” Dr. Korngold said.
A version of this article appeared on Medscape.com.
LONG BEACH, CALIFORNIA — A small fraction of patients with pulmonary embolism (PE) who are eligible for advanced therapies are actually getting them, reported investigators who conducted a big data analysis.
“Advanced PE therapy seems to be vulnerable to disparate use, and perhaps underuse,” Sahil Parikh, MD, a cardiovascular interventionalist at the Columbia University Medical Center in New York, said when he presented results from the REAL-PE study at the Society for Cardiovascular Angiography and Interventions (SCAI) 2024 Scientific Sessions.
The underuse of advanced PE therapies is “the controversy,” Dr. Parikh said after his presentation. “It remains unclear what the role of invasive therapy is in the management of so-called high-intermediate–risk people. There isn’t a Class 1 guideline recommendation, and there is a very rapidly evolving trend that we’re increasingly treating these patients invasively,” he said.
“However, if you come to these meetings [such as SCAI], you might think everyone is getting one of these devices, but these data show that’s not the case,” Dr. Parikh said.
The analysis mined deidentified data from Truveta, a collective of health systems that provides regulatory-grade electronic health record data for research.
The researchers accessed data on patients treated with ultrasound-assisted catheter-directed thrombolysis or mechanical thrombectomy, identified from claims codes. Patient characteristics — age, race, ethnicity, sex, comorbidities, and diagnoses — were also accessed for the analysis. Earlier results were published in the January issue of the Journal of the Society for Cardiovascular Angioplasty Interventions.
Less Intervention for Black Patients and Women
White patients were more likely to receive advanced therapy than were Black patients (0.5% vs 0.37%; P = .000), Dr. Parikh reported, and women were less likely to receive advanced therapy than were men (0.41% vs 0.55%; P = .000).
The only discernable differences in outcomes were in major bleeding events in the 7 days after the procedure, which affected more White patients than it did Black patients (13.9% vs 9.3%) and affected more women than it did men (16.6% vs 11.1%).
What’s noteworthy about this study is that it demonstrates the potential of advanced data analytics to identify disparities in care and outcomes, Dr. Parikh said during his presentation. “These analyses provide a means of evaluating disparities in real clinical practice, both in the area of PE and otherwise, and may also be used for real-time monitoring of clinical decision-making and decisional support,” he said. “We do think that both novel and established therapies can benefit equally from similar types of analyses.”
Big Data Signaling Disparities
“That’s where these data are helpful,” Dr. Parikh explained. They provide “a real snapshot of how many procedures are being performed and in what kinds of patients. The low number of patients getting the procedure would suggest that there are probably more patients who would be eligible for treatment based on some of the emerging consensus documents, and they’re not receiving them.”
The data are “hypotheses generating,” Dr. Parikh said in an interview. “These hypotheses have to be evaluated further in more granular databases.”
REAL-PE is also a “clarion call” for clinical trials of investigative devices going forward, he said. “In those trials, we need to endeavor to enroll enough women and men, minority and nonminority patients so that we can make meaningful assessments of differences in efficacy and safety.”
This study is “real proof that big data can be used to provide information on outcomes for patients in a very rapid manner; that’s really exciting,” said Ethan Korngold, MD, chair of structural and interventional cardiology at the Providence Health Institute in Portland, Oregon. “This is an area of great research with great innovation, and it’s proof that, with these type of techniques using artificial intelligence and big data, we can generate data quickly on how we’re doing and what kind of patients we’re reaching.”
Findings like these may also help identify sources of the disparities, Dr. Korngold added.
“This shows we need to be reaching every patient with advanced therapies,” he said. “Different hospitals have different capabilities and different expertise in this area and they reach different patient populations. A lot of the difference in utilization stems from this fact,” he said.
“It just underscores the fact that we need to standardize our treatment approaches, and then we need to reach every person who’s suffering from this disease,” Dr. Korngold said.
A version of this article appeared on Medscape.com.
LONG BEACH, CALIFORNIA — A small fraction of patients with pulmonary embolism (PE) who are eligible for advanced therapies are actually getting them, reported investigators who conducted a big data analysis.
“Advanced PE therapy seems to be vulnerable to disparate use, and perhaps underuse,” Sahil Parikh, MD, a cardiovascular interventionalist at the Columbia University Medical Center in New York, said when he presented results from the REAL-PE study at the Society for Cardiovascular Angiography and Interventions (SCAI) 2024 Scientific Sessions.
The underuse of advanced PE therapies is “the controversy,” Dr. Parikh said after his presentation. “It remains unclear what the role of invasive therapy is in the management of so-called high-intermediate–risk people. There isn’t a Class 1 guideline recommendation, and there is a very rapidly evolving trend that we’re increasingly treating these patients invasively,” he said.
“However, if you come to these meetings [such as SCAI], you might think everyone is getting one of these devices, but these data show that’s not the case,” Dr. Parikh said.
The analysis mined deidentified data from Truveta, a collective of health systems that provides regulatory-grade electronic health record data for research.
The researchers accessed data on patients treated with ultrasound-assisted catheter-directed thrombolysis or mechanical thrombectomy, identified from claims codes. Patient characteristics — age, race, ethnicity, sex, comorbidities, and diagnoses — were also accessed for the analysis. Earlier results were published in the January issue of the Journal of the Society for Cardiovascular Angioplasty Interventions.
Less Intervention for Black Patients and Women
White patients were more likely to receive advanced therapy than were Black patients (0.5% vs 0.37%; P = .000), Dr. Parikh reported, and women were less likely to receive advanced therapy than were men (0.41% vs 0.55%; P = .000).
The only discernable differences in outcomes were in major bleeding events in the 7 days after the procedure, which affected more White patients than it did Black patients (13.9% vs 9.3%) and affected more women than it did men (16.6% vs 11.1%).
What’s noteworthy about this study is that it demonstrates the potential of advanced data analytics to identify disparities in care and outcomes, Dr. Parikh said during his presentation. “These analyses provide a means of evaluating disparities in real clinical practice, both in the area of PE and otherwise, and may also be used for real-time monitoring of clinical decision-making and decisional support,” he said. “We do think that both novel and established therapies can benefit equally from similar types of analyses.”
Big Data Signaling Disparities
“That’s where these data are helpful,” Dr. Parikh explained. They provide “a real snapshot of how many procedures are being performed and in what kinds of patients. The low number of patients getting the procedure would suggest that there are probably more patients who would be eligible for treatment based on some of the emerging consensus documents, and they’re not receiving them.”
The data are “hypotheses generating,” Dr. Parikh said in an interview. “These hypotheses have to be evaluated further in more granular databases.”
REAL-PE is also a “clarion call” for clinical trials of investigative devices going forward, he said. “In those trials, we need to endeavor to enroll enough women and men, minority and nonminority patients so that we can make meaningful assessments of differences in efficacy and safety.”
This study is “real proof that big data can be used to provide information on outcomes for patients in a very rapid manner; that’s really exciting,” said Ethan Korngold, MD, chair of structural and interventional cardiology at the Providence Health Institute in Portland, Oregon. “This is an area of great research with great innovation, and it’s proof that, with these type of techniques using artificial intelligence and big data, we can generate data quickly on how we’re doing and what kind of patients we’re reaching.”
Findings like these may also help identify sources of the disparities, Dr. Korngold added.
“This shows we need to be reaching every patient with advanced therapies,” he said. “Different hospitals have different capabilities and different expertise in this area and they reach different patient populations. A lot of the difference in utilization stems from this fact,” he said.
“It just underscores the fact that we need to standardize our treatment approaches, and then we need to reach every person who’s suffering from this disease,” Dr. Korngold said.
A version of this article appeared on Medscape.com.
New Oral Weight Loss Drugs: Where Are We and What’s Next?
, in line with patient preference.
One particularly intriguing entry is ARD-101, in development by Aardvark Therapeutics in San Diego, California. Aardvark came out of stealth on May 9 with the announcement of $85 million in new financing. The biopharma will use the money to complete trials of ARD-101 to treat hyperphagia in Prader-Willi syndrome, both to help patients quell the unrelenting hunger that characterizes the orphan disease and as a proof of principle to demonstrate the compound’s complementary mechanism of action to the current glucagon-like peptide 1 (GLP-1) therapies for obesity.
Oral ARD-101 is a bitter taste receptor (TAS2R) that mediates hunger, whereas the GLP-1 drugs mainly influence appetite, said the company’s CEO, Tien Lee, MD.
“If you love chocolate cake, for instance, appetite is driving you to eat that. And if that chocolate cake were to turn magically into dog food, your appetite probably would go to zero. But if that dog food were your only food source, over enough time, hunger would eventually compel you to eat it. That’s how they’re differentially driven.”
He added, “Hunger and appetite approaches are not mutually exclusive. In fact, they’re complementary to each other, and they’re additive in terms of treatment effect.”
Now that the company is out of stealth, expect more published data and updates on ongoing studies, he added.
Here’s a look at other promising oral drugs on the horizon.
Oral Semaglutide
The once-daily 50 mg tablet formulation of this GLP-1 receptor agonist is among the nearest to approval. The formulation was studied for weight loss in individuals with overweight/obesity in the OASIS 1 phase 3a trial. When applying the treatment policy estimand (defined as the treatment effect regardless of adherence), people who took the pill achieved a weight loss of 15.1% over 68 weeks compared with a 2.4% reduction with placebo, and 84.9% achieved a weight loss of ≥ 5% vs 25.8% with placebo, according to the manufacturer Novo Nordisk.
A spokesperson for the company told this news organization that, contrary to earlier reports, the 50 mg pill will be submitted for regulatory approval after results from OASIS 4 are in, “so we have the full data set.” OASIS 4 is investigating the 25 mg oral dose, and results are expected this year.
“The US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity,” the spokesperson said. The company can produce semaglutide as a tablet or injectable, but the oral form requires more an active pharmaceutical ingredient. Therefore, production capacities are being expanded globally for both formulations.
Oral Amycretin
Novo Nordisk’s spokesperson said that, as announced in March, results from an exploratory endpoint on body weight change in a phase 1 trial showed an average −13.1% reduction after 12 weeks of treatment with once-daily oral amycretin compared with −1.1% for placebo. The favorable safety/tolerability and pharmacokinetic profile observed in the trial allows for further development of amycretin.
“Moreover,” the spokesperson said, “we are developing the oral small molecule CB1 receptor inverse agonist monlunabant (INV-202), which has shown weight loss potential in phase 1 with a favorable safety and tolerability profile and is currently being investigated in phase 2 in diabetic kidney disease and obesity.”
APH-012
As of April 25, Aphaia Pharma completed enrollment of the first two cohorts in its randomized, double-blind, placebo-controlled proof-of-concept phase 2 trial evaluating a once-daily 12-g dose of its proprietary oral glucose formulation APHD-12 for obesity.
The company also announced that the US Food and Drug Administration (FDA) has approved an expansion of the trial›s protocol to investigate the contribution of circadian effects in weight loss treatment. The new protocol will include additional cohorts, which will be dosed with either 6 g (APHD-006) or 8 g (APHD-008) of Aphaia’s formulation or placebos twice daily. The primary endpoint of the trial is the change from baseline in percent weight compared with placebo. The study will also evaluate exploratory secondary endpoints, which are considered hallmarks of multiple metabolic diseases closely associated with obesity.
The drug candidate is “designed to be released at discrete parts of the small intestine to restore endogenous nutrient-sensing signaling pathways and stimulate the release of the broad spectrum of enteric hormones that control multiple homeostatic functions like appetite, hunger, satiety, glucose metabolism, and energy expenditure,” according to the company’s announcement. “This includes glucagon-like peptide 1, peptide tyrosine-tyrosine, glicentin, and oxyntomodulin, among others.”
Topline data from the first part of the study are expected to be released by the third quarter.
AZD5004
In November 2023, AstraZeneca entered into an exclusive licensing agreement with Eccogene to develop and commercialize ECC5004 (now AZD5004), a tablet formulation of a small molecule GLP-1 receptor agonist, both as monotherapy and in combination with AZD6234, its antiobesity agent that targets the gut hormone amylin.
“We are excited by the potential of AZD5004 as a novel oral small molecule GLP-1 receptor agonist,” a company spokesperson told this news organization. “The phase 1 study has provided us with the confidence to progress development into a phase 2 program studying patients with type 2 diabetes and in obesity. We are in the process of designing these studies and expect to start them in the second half of 2024.”
Ecnoglutide
In January, Sciwind Biosciences announced positive interim results from the first four cohorts of a phase 1 clinical trial of oral ecnoglutide (XW004). Ecnoglutide is a long-acting, cAMP signaling biased, GLP-1 analog being developed for the treatment of obesity and type 2 diabetes.
The phase 1 trial (NCT05184322) is a randomized, double-blind, placebo-controlled multiple ascending dose study that enrolled 42 healthy (cohorts 1-3) and 14 healthy obese (cohort 4) participants in Australia. In cohorts 1-3, target doses were 7 mg, 15 mg, or 30 mg XW004 once daily for 2 weeks; in cohort 4, the target dose was 30 mg XW004 once daily for 6 weeks. Treatment periods included gradual dose escalation to the target doses.
Study participants achieved a mean body weight reduction of −6.8% from baseline, compared with −0.9% for the placebo group, according to the company. Based on the positive results, the study is continuing and will evaluate additional dosing regimens, including once-weekly oral administration in participants with obesity.
The company is also developing an injectable formulation of ecnoglutide.
GSBR-1290
On May 9, Structure Therapeutics released highlights of the company›s evaluation of GSBR-1290, an oral small molecule selective GLP-1 receptor agonist. Topline data from the obesity cohort of the phase 2a study, including 12-week efficacy data for 40 participants and safety and tolerability for all 64 participants, are expected in June.
In preparation for later stage clinical trials, the company said it is conducting a formulation bridging and titration study to evaluate capsule vs tablet pharmacokinetics and explore different titration regimens of the molecule. Pharmacokinetic study results are also expected in June.
A global phase 2b obesity study is planned for the fourth quarter of 2024.
Orforglipron
Orforglipron is an oral GLP-1 receptor agonist being developed by Eli Lilly and Co. A phase 3 study of the once-daily capsule is underway, and will run until mid-2027.
Phase 2 data presented last year at the American Diabetes Association conference 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.
Additionally, a meta-analysis of randomized controlled trials of the drug was recently published.
A Lilly spokesperson told this news organization that phase 3 results from the ATTAIN-1 study are “expected to be to be available beginning in 2025, and we can expect a launch possibly a year after that.”
VK2735
VK2735, a dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, is being developed by Viking Therapeutics for the treatment of metabolic disorders, including obesity, in both subcutaneous and oral formulations.
In a phase 1, 28-day multiple ascending dose study, cohorts receiving oral formulation VK2735 had dose-dependent reductions in mean body weight from baseline, ranging up to 5.3%, and also demonstrated reductions in mean body weight relative to placebo, ranging up to 3.3%. For doses ≥ 10 mg, placebo-adjusted reductions in mean body weight were maintained or improved at day 34, 6 days after the last dose of VK2735 was administered, ranging up to 3.6% relative to placebo.
Based on these phase 1 results, the company plans to initiate a phase 2 trial in obesity later this year.
A version of this article appeared on Medscape.com.
, in line with patient preference.
One particularly intriguing entry is ARD-101, in development by Aardvark Therapeutics in San Diego, California. Aardvark came out of stealth on May 9 with the announcement of $85 million in new financing. The biopharma will use the money to complete trials of ARD-101 to treat hyperphagia in Prader-Willi syndrome, both to help patients quell the unrelenting hunger that characterizes the orphan disease and as a proof of principle to demonstrate the compound’s complementary mechanism of action to the current glucagon-like peptide 1 (GLP-1) therapies for obesity.
Oral ARD-101 is a bitter taste receptor (TAS2R) that mediates hunger, whereas the GLP-1 drugs mainly influence appetite, said the company’s CEO, Tien Lee, MD.
“If you love chocolate cake, for instance, appetite is driving you to eat that. And if that chocolate cake were to turn magically into dog food, your appetite probably would go to zero. But if that dog food were your only food source, over enough time, hunger would eventually compel you to eat it. That’s how they’re differentially driven.”
He added, “Hunger and appetite approaches are not mutually exclusive. In fact, they’re complementary to each other, and they’re additive in terms of treatment effect.”
Now that the company is out of stealth, expect more published data and updates on ongoing studies, he added.
Here’s a look at other promising oral drugs on the horizon.
Oral Semaglutide
The once-daily 50 mg tablet formulation of this GLP-1 receptor agonist is among the nearest to approval. The formulation was studied for weight loss in individuals with overweight/obesity in the OASIS 1 phase 3a trial. When applying the treatment policy estimand (defined as the treatment effect regardless of adherence), people who took the pill achieved a weight loss of 15.1% over 68 weeks compared with a 2.4% reduction with placebo, and 84.9% achieved a weight loss of ≥ 5% vs 25.8% with placebo, according to the manufacturer Novo Nordisk.
A spokesperson for the company told this news organization that, contrary to earlier reports, the 50 mg pill will be submitted for regulatory approval after results from OASIS 4 are in, “so we have the full data set.” OASIS 4 is investigating the 25 mg oral dose, and results are expected this year.
“The US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity,” the spokesperson said. The company can produce semaglutide as a tablet or injectable, but the oral form requires more an active pharmaceutical ingredient. Therefore, production capacities are being expanded globally for both formulations.
Oral Amycretin
Novo Nordisk’s spokesperson said that, as announced in March, results from an exploratory endpoint on body weight change in a phase 1 trial showed an average −13.1% reduction after 12 weeks of treatment with once-daily oral amycretin compared with −1.1% for placebo. The favorable safety/tolerability and pharmacokinetic profile observed in the trial allows for further development of amycretin.
“Moreover,” the spokesperson said, “we are developing the oral small molecule CB1 receptor inverse agonist monlunabant (INV-202), which has shown weight loss potential in phase 1 with a favorable safety and tolerability profile and is currently being investigated in phase 2 in diabetic kidney disease and obesity.”
APH-012
As of April 25, Aphaia Pharma completed enrollment of the first two cohorts in its randomized, double-blind, placebo-controlled proof-of-concept phase 2 trial evaluating a once-daily 12-g dose of its proprietary oral glucose formulation APHD-12 for obesity.
The company also announced that the US Food and Drug Administration (FDA) has approved an expansion of the trial›s protocol to investigate the contribution of circadian effects in weight loss treatment. The new protocol will include additional cohorts, which will be dosed with either 6 g (APHD-006) or 8 g (APHD-008) of Aphaia’s formulation or placebos twice daily. The primary endpoint of the trial is the change from baseline in percent weight compared with placebo. The study will also evaluate exploratory secondary endpoints, which are considered hallmarks of multiple metabolic diseases closely associated with obesity.
The drug candidate is “designed to be released at discrete parts of the small intestine to restore endogenous nutrient-sensing signaling pathways and stimulate the release of the broad spectrum of enteric hormones that control multiple homeostatic functions like appetite, hunger, satiety, glucose metabolism, and energy expenditure,” according to the company’s announcement. “This includes glucagon-like peptide 1, peptide tyrosine-tyrosine, glicentin, and oxyntomodulin, among others.”
Topline data from the first part of the study are expected to be released by the third quarter.
AZD5004
In November 2023, AstraZeneca entered into an exclusive licensing agreement with Eccogene to develop and commercialize ECC5004 (now AZD5004), a tablet formulation of a small molecule GLP-1 receptor agonist, both as monotherapy and in combination with AZD6234, its antiobesity agent that targets the gut hormone amylin.
“We are excited by the potential of AZD5004 as a novel oral small molecule GLP-1 receptor agonist,” a company spokesperson told this news organization. “The phase 1 study has provided us with the confidence to progress development into a phase 2 program studying patients with type 2 diabetes and in obesity. We are in the process of designing these studies and expect to start them in the second half of 2024.”
Ecnoglutide
In January, Sciwind Biosciences announced positive interim results from the first four cohorts of a phase 1 clinical trial of oral ecnoglutide (XW004). Ecnoglutide is a long-acting, cAMP signaling biased, GLP-1 analog being developed for the treatment of obesity and type 2 diabetes.
The phase 1 trial (NCT05184322) is a randomized, double-blind, placebo-controlled multiple ascending dose study that enrolled 42 healthy (cohorts 1-3) and 14 healthy obese (cohort 4) participants in Australia. In cohorts 1-3, target doses were 7 mg, 15 mg, or 30 mg XW004 once daily for 2 weeks; in cohort 4, the target dose was 30 mg XW004 once daily for 6 weeks. Treatment periods included gradual dose escalation to the target doses.
Study participants achieved a mean body weight reduction of −6.8% from baseline, compared with −0.9% for the placebo group, according to the company. Based on the positive results, the study is continuing and will evaluate additional dosing regimens, including once-weekly oral administration in participants with obesity.
The company is also developing an injectable formulation of ecnoglutide.
GSBR-1290
On May 9, Structure Therapeutics released highlights of the company›s evaluation of GSBR-1290, an oral small molecule selective GLP-1 receptor agonist. Topline data from the obesity cohort of the phase 2a study, including 12-week efficacy data for 40 participants and safety and tolerability for all 64 participants, are expected in June.
In preparation for later stage clinical trials, the company said it is conducting a formulation bridging and titration study to evaluate capsule vs tablet pharmacokinetics and explore different titration regimens of the molecule. Pharmacokinetic study results are also expected in June.
A global phase 2b obesity study is planned for the fourth quarter of 2024.
Orforglipron
Orforglipron is an oral GLP-1 receptor agonist being developed by Eli Lilly and Co. A phase 3 study of the once-daily capsule is underway, and will run until mid-2027.
Phase 2 data presented last year at the American Diabetes Association conference 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.
Additionally, a meta-analysis of randomized controlled trials of the drug was recently published.
A Lilly spokesperson told this news organization that phase 3 results from the ATTAIN-1 study are “expected to be to be available beginning in 2025, and we can expect a launch possibly a year after that.”
VK2735
VK2735, a dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, is being developed by Viking Therapeutics for the treatment of metabolic disorders, including obesity, in both subcutaneous and oral formulations.
In a phase 1, 28-day multiple ascending dose study, cohorts receiving oral formulation VK2735 had dose-dependent reductions in mean body weight from baseline, ranging up to 5.3%, and also demonstrated reductions in mean body weight relative to placebo, ranging up to 3.3%. For doses ≥ 10 mg, placebo-adjusted reductions in mean body weight were maintained or improved at day 34, 6 days after the last dose of VK2735 was administered, ranging up to 3.6% relative to placebo.
Based on these phase 1 results, the company plans to initiate a phase 2 trial in obesity later this year.
A version of this article appeared on Medscape.com.
, in line with patient preference.
One particularly intriguing entry is ARD-101, in development by Aardvark Therapeutics in San Diego, California. Aardvark came out of stealth on May 9 with the announcement of $85 million in new financing. The biopharma will use the money to complete trials of ARD-101 to treat hyperphagia in Prader-Willi syndrome, both to help patients quell the unrelenting hunger that characterizes the orphan disease and as a proof of principle to demonstrate the compound’s complementary mechanism of action to the current glucagon-like peptide 1 (GLP-1) therapies for obesity.
Oral ARD-101 is a bitter taste receptor (TAS2R) that mediates hunger, whereas the GLP-1 drugs mainly influence appetite, said the company’s CEO, Tien Lee, MD.
“If you love chocolate cake, for instance, appetite is driving you to eat that. And if that chocolate cake were to turn magically into dog food, your appetite probably would go to zero. But if that dog food were your only food source, over enough time, hunger would eventually compel you to eat it. That’s how they’re differentially driven.”
He added, “Hunger and appetite approaches are not mutually exclusive. In fact, they’re complementary to each other, and they’re additive in terms of treatment effect.”
Now that the company is out of stealth, expect more published data and updates on ongoing studies, he added.
Here’s a look at other promising oral drugs on the horizon.
Oral Semaglutide
The once-daily 50 mg tablet formulation of this GLP-1 receptor agonist is among the nearest to approval. The formulation was studied for weight loss in individuals with overweight/obesity in the OASIS 1 phase 3a trial. When applying the treatment policy estimand (defined as the treatment effect regardless of adherence), people who took the pill achieved a weight loss of 15.1% over 68 weeks compared with a 2.4% reduction with placebo, and 84.9% achieved a weight loss of ≥ 5% vs 25.8% with placebo, according to the manufacturer Novo Nordisk.
A spokesperson for the company told this news organization that, contrary to earlier reports, the 50 mg pill will be submitted for regulatory approval after results from OASIS 4 are in, “so we have the full data set.” OASIS 4 is investigating the 25 mg oral dose, and results are expected this year.
“The US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity,” the spokesperson said. The company can produce semaglutide as a tablet or injectable, but the oral form requires more an active pharmaceutical ingredient. Therefore, production capacities are being expanded globally for both formulations.
Oral Amycretin
Novo Nordisk’s spokesperson said that, as announced in March, results from an exploratory endpoint on body weight change in a phase 1 trial showed an average −13.1% reduction after 12 weeks of treatment with once-daily oral amycretin compared with −1.1% for placebo. The favorable safety/tolerability and pharmacokinetic profile observed in the trial allows for further development of amycretin.
“Moreover,” the spokesperson said, “we are developing the oral small molecule CB1 receptor inverse agonist monlunabant (INV-202), which has shown weight loss potential in phase 1 with a favorable safety and tolerability profile and is currently being investigated in phase 2 in diabetic kidney disease and obesity.”
APH-012
As of April 25, Aphaia Pharma completed enrollment of the first two cohorts in its randomized, double-blind, placebo-controlled proof-of-concept phase 2 trial evaluating a once-daily 12-g dose of its proprietary oral glucose formulation APHD-12 for obesity.
The company also announced that the US Food and Drug Administration (FDA) has approved an expansion of the trial›s protocol to investigate the contribution of circadian effects in weight loss treatment. The new protocol will include additional cohorts, which will be dosed with either 6 g (APHD-006) or 8 g (APHD-008) of Aphaia’s formulation or placebos twice daily. The primary endpoint of the trial is the change from baseline in percent weight compared with placebo. The study will also evaluate exploratory secondary endpoints, which are considered hallmarks of multiple metabolic diseases closely associated with obesity.
The drug candidate is “designed to be released at discrete parts of the small intestine to restore endogenous nutrient-sensing signaling pathways and stimulate the release of the broad spectrum of enteric hormones that control multiple homeostatic functions like appetite, hunger, satiety, glucose metabolism, and energy expenditure,” according to the company’s announcement. “This includes glucagon-like peptide 1, peptide tyrosine-tyrosine, glicentin, and oxyntomodulin, among others.”
Topline data from the first part of the study are expected to be released by the third quarter.
AZD5004
In November 2023, AstraZeneca entered into an exclusive licensing agreement with Eccogene to develop and commercialize ECC5004 (now AZD5004), a tablet formulation of a small molecule GLP-1 receptor agonist, both as monotherapy and in combination with AZD6234, its antiobesity agent that targets the gut hormone amylin.
“We are excited by the potential of AZD5004 as a novel oral small molecule GLP-1 receptor agonist,” a company spokesperson told this news organization. “The phase 1 study has provided us with the confidence to progress development into a phase 2 program studying patients with type 2 diabetes and in obesity. We are in the process of designing these studies and expect to start them in the second half of 2024.”
Ecnoglutide
In January, Sciwind Biosciences announced positive interim results from the first four cohorts of a phase 1 clinical trial of oral ecnoglutide (XW004). Ecnoglutide is a long-acting, cAMP signaling biased, GLP-1 analog being developed for the treatment of obesity and type 2 diabetes.
The phase 1 trial (NCT05184322) is a randomized, double-blind, placebo-controlled multiple ascending dose study that enrolled 42 healthy (cohorts 1-3) and 14 healthy obese (cohort 4) participants in Australia. In cohorts 1-3, target doses were 7 mg, 15 mg, or 30 mg XW004 once daily for 2 weeks; in cohort 4, the target dose was 30 mg XW004 once daily for 6 weeks. Treatment periods included gradual dose escalation to the target doses.
Study participants achieved a mean body weight reduction of −6.8% from baseline, compared with −0.9% for the placebo group, according to the company. Based on the positive results, the study is continuing and will evaluate additional dosing regimens, including once-weekly oral administration in participants with obesity.
The company is also developing an injectable formulation of ecnoglutide.
GSBR-1290
On May 9, Structure Therapeutics released highlights of the company›s evaluation of GSBR-1290, an oral small molecule selective GLP-1 receptor agonist. Topline data from the obesity cohort of the phase 2a study, including 12-week efficacy data for 40 participants and safety and tolerability for all 64 participants, are expected in June.
In preparation for later stage clinical trials, the company said it is conducting a formulation bridging and titration study to evaluate capsule vs tablet pharmacokinetics and explore different titration regimens of the molecule. Pharmacokinetic study results are also expected in June.
A global phase 2b obesity study is planned for the fourth quarter of 2024.
Orforglipron
Orforglipron is an oral GLP-1 receptor agonist being developed by Eli Lilly and Co. A phase 3 study of the once-daily capsule is underway, and will run until mid-2027.
Phase 2 data presented last year at the American Diabetes Association conference 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.
Additionally, a meta-analysis of randomized controlled trials of the drug was recently published.
A Lilly spokesperson told this news organization that phase 3 results from the ATTAIN-1 study are “expected to be to be available beginning in 2025, and we can expect a launch possibly a year after that.”
VK2735
VK2735, a dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, is being developed by Viking Therapeutics for the treatment of metabolic disorders, including obesity, in both subcutaneous and oral formulations.
In a phase 1, 28-day multiple ascending dose study, cohorts receiving oral formulation VK2735 had dose-dependent reductions in mean body weight from baseline, ranging up to 5.3%, and also demonstrated reductions in mean body weight relative to placebo, ranging up to 3.3%. For doses ≥ 10 mg, placebo-adjusted reductions in mean body weight were maintained or improved at day 34, 6 days after the last dose of VK2735 was administered, ranging up to 3.6% relative to placebo.
Based on these phase 1 results, the company plans to initiate a phase 2 trial in obesity later this year.
A version of this article appeared on Medscape.com.
Over-the-Counter Arthritis Supplements Pose Adrenal Danger
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
Age, Race, and Insurance Status May Effect Initial Sarcoidosis Severity
presented at the American Thoracic Society’s International Conference 2024.
“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.
Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.
No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.
“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.
For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.
“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
Pinpointing Persistent Disparities
“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.
The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.
“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.
Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.
In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.
The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
presented at the American Thoracic Society’s International Conference 2024.
“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.
Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.
No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.
“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.
For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.
“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
Pinpointing Persistent Disparities
“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.
The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.
“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.
Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.
In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.
The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
presented at the American Thoracic Society’s International Conference 2024.
“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.
Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.
No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.
“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.
For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.
“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
Pinpointing Persistent Disparities
“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.
The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.
“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.
Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.
In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.
The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Who Benefits From Omega-3/Fish Oil Supplements?
I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).
This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.
Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.
For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.
The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.
What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.
What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American.
There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.
Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.
A version of this article appeared on Medscape.com.
I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).
This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.
Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.
For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.
The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.
What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.
What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American.
There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.
Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.
A version of this article appeared on Medscape.com.
I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).
This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.
Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.
For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.
The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.
What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.
What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American.
There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.
Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.
A version of this article appeared on Medscape.com.
Moderna’s RSV Vaccine Approved by FDA
The US Food and Drug Administration (FDA) approved mRESVIA (mRNA-1345, Moderna), a vaccine for respiratory syncytial virus (RSV).
“The FDA approval of our second product, mRESVIA, builds on the strength and versatility of our mRNA platform,” Stéphane Bancel, chief executive officer of Moderna, said in a news release. “mRESVIA protects older adults from the severe outcomes of RSV infection. This approval is also the first time an mRNA vaccine has been approved for a disease other than COVID-19.”
mRESVIA is a single-dose vaccine available in prefilled syringes, which the company says are designed to maximize ease of administration, saving vaccinators’ time, and reducing the risk for administrative errors.
The approval is based on the positive results from the phase 3 ConquerRSV clinical trial, published in The New England Journal of Medicine in December 2023. The study, conducted in approximately 37,000 adults aged 60 years or older in 22 countries, found a vaccine efficacy against RSV lower respiratory tract disease of 83.7% after a median 3.7 months of follow-up.
An additional longer-term analysis showed continued protection over 8.6 months median follow-up. No serious safety concerns were identified. The most reported adverse reactions were injection site pain, fatigue, headache, myalgia, and arthralgia.
Moderna has also filed for approval in multiple markets around the world, and says it expects mRESVIA to be available in the United States in time for the 2024-2025 respiratory virus season.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) approved mRESVIA (mRNA-1345, Moderna), a vaccine for respiratory syncytial virus (RSV).
“The FDA approval of our second product, mRESVIA, builds on the strength and versatility of our mRNA platform,” Stéphane Bancel, chief executive officer of Moderna, said in a news release. “mRESVIA protects older adults from the severe outcomes of RSV infection. This approval is also the first time an mRNA vaccine has been approved for a disease other than COVID-19.”
mRESVIA is a single-dose vaccine available in prefilled syringes, which the company says are designed to maximize ease of administration, saving vaccinators’ time, and reducing the risk for administrative errors.
The approval is based on the positive results from the phase 3 ConquerRSV clinical trial, published in The New England Journal of Medicine in December 2023. The study, conducted in approximately 37,000 adults aged 60 years or older in 22 countries, found a vaccine efficacy against RSV lower respiratory tract disease of 83.7% after a median 3.7 months of follow-up.
An additional longer-term analysis showed continued protection over 8.6 months median follow-up. No serious safety concerns were identified. The most reported adverse reactions were injection site pain, fatigue, headache, myalgia, and arthralgia.
Moderna has also filed for approval in multiple markets around the world, and says it expects mRESVIA to be available in the United States in time for the 2024-2025 respiratory virus season.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) approved mRESVIA (mRNA-1345, Moderna), a vaccine for respiratory syncytial virus (RSV).
“The FDA approval of our second product, mRESVIA, builds on the strength and versatility of our mRNA platform,” Stéphane Bancel, chief executive officer of Moderna, said in a news release. “mRESVIA protects older adults from the severe outcomes of RSV infection. This approval is also the first time an mRNA vaccine has been approved for a disease other than COVID-19.”
mRESVIA is a single-dose vaccine available in prefilled syringes, which the company says are designed to maximize ease of administration, saving vaccinators’ time, and reducing the risk for administrative errors.
The approval is based on the positive results from the phase 3 ConquerRSV clinical trial, published in The New England Journal of Medicine in December 2023. The study, conducted in approximately 37,000 adults aged 60 years or older in 22 countries, found a vaccine efficacy against RSV lower respiratory tract disease of 83.7% after a median 3.7 months of follow-up.
An additional longer-term analysis showed continued protection over 8.6 months median follow-up. No serious safety concerns were identified. The most reported adverse reactions were injection site pain, fatigue, headache, myalgia, and arthralgia.
Moderna has also filed for approval in multiple markets around the world, and says it expects mRESVIA to be available in the United States in time for the 2024-2025 respiratory virus season.
A version of this article appeared on Medscape.com.
Anti-Müllerian Hormone Predicts Chemo Benefits in BC
The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.
“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).
The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
New Analysis Singles Out AMH Levels
In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.
The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.
The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).
To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.
The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.
Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.
A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.
Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).
In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.
Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).
The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.
During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
AMH May Ultimately Inform Chemotherapy Choices
The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.
Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.
As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.
Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.
Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
Clinical Challenges of Menopausal Status
Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.
“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.
“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.
“My hope is that new data allow for a more informed, individualized decision-making process,” she added.
Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.
Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.
“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.
In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.
The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.
Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.
Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.
Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.
Dr. West had no financial conflicts to disclose.
The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.
“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).
The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
New Analysis Singles Out AMH Levels
In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.
The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.
The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).
To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.
The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.
Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.
A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.
Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).
In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.
Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).
The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.
During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
AMH May Ultimately Inform Chemotherapy Choices
The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.
Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.
As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.
Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.
Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
Clinical Challenges of Menopausal Status
Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.
“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.
“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.
“My hope is that new data allow for a more informed, individualized decision-making process,” she added.
Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.
Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.
“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.
In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.
The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.
Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.
Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.
Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.
Dr. West had no financial conflicts to disclose.
The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.
“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).
The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
New Analysis Singles Out AMH Levels
In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.
The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.
The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).
To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.
The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.
Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.
A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.
Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).
In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.
Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).
The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.
During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
AMH May Ultimately Inform Chemotherapy Choices
The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.
Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.
As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.
Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.
Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
Clinical Challenges of Menopausal Status
Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.
“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.
“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.
“My hope is that new data allow for a more informed, individualized decision-making process,” she added.
Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.
Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.
“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.
In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.
The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.
Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.
Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.
Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.
Dr. West had no financial conflicts to disclose.
FROM ASCO 2024
Internists Feel Underpaid, But Job Satisfaction Persists
A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.
Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.
The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.
Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.
Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.
Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”
In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.
More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
Regular Pay Assessment Increases Awareness
Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.
“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
Job Satisfaction Remains Important
As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.
“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.
“I would have picked internal medicine because of the satisfaction that it brings me,” he said.
Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.
Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.
A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.
Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.
The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.
Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.
Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.
Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”
In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.
More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
Regular Pay Assessment Increases Awareness
Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.
“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
Job Satisfaction Remains Important
As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.
“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.
“I would have picked internal medicine because of the satisfaction that it brings me,” he said.
Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.
Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.
A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.
Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.
The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.
Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.
Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.
Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”
In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.
More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
Regular Pay Assessment Increases Awareness
Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.
“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
Job Satisfaction Remains Important
As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.
“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.
“I would have picked internal medicine because of the satisfaction that it brings me,” he said.
Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.
Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.