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FDA Approves OnabotulinumtoxinA for Improving Platysma Bands
The in adults.
According to a press release from Allergan Aesthetics, which developed onabotulinumtoxinA, by injecting along the jawline and the vertical bands connecting the jaw and neck with one of the FDA-approved doses of the product based on severity, onabotulinumtoxinA temporarily reduces underlying muscle activity.
The company cited results from phase 3 clinical studies, which demonstrated statistical significance for the improvement in appearance of platysma bands from baseline with onabotulinumtoxinA compared with placebo on both investigator and patient assessment (P < .0001).
All secondary endpoints were also met, as measured by multiple validated, proprietary patient-reported outcome instruments. In two of the clinical studies, for example, 65% and 62% of patients reported being “very satisfied” or “satisfied,” respectively, with their neck and jawline definition 14 days after treatment with a dose of 26, 31, or 36 units of onabotulinumtoxinA, compared with 12% with placebo in both studies.
The development marks the fourth indication for onabotulinumtoxinA. The others are for moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity, moderate to severe lateral canthal lines associated with orbicularis oculi activity, and moderate to severe forehead lines associated with frontalis activity.
A version of this article appeared on Medscape.com.
The in adults.
According to a press release from Allergan Aesthetics, which developed onabotulinumtoxinA, by injecting along the jawline and the vertical bands connecting the jaw and neck with one of the FDA-approved doses of the product based on severity, onabotulinumtoxinA temporarily reduces underlying muscle activity.
The company cited results from phase 3 clinical studies, which demonstrated statistical significance for the improvement in appearance of platysma bands from baseline with onabotulinumtoxinA compared with placebo on both investigator and patient assessment (P < .0001).
All secondary endpoints were also met, as measured by multiple validated, proprietary patient-reported outcome instruments. In two of the clinical studies, for example, 65% and 62% of patients reported being “very satisfied” or “satisfied,” respectively, with their neck and jawline definition 14 days after treatment with a dose of 26, 31, or 36 units of onabotulinumtoxinA, compared with 12% with placebo in both studies.
The development marks the fourth indication for onabotulinumtoxinA. The others are for moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity, moderate to severe lateral canthal lines associated with orbicularis oculi activity, and moderate to severe forehead lines associated with frontalis activity.
A version of this article appeared on Medscape.com.
The in adults.
According to a press release from Allergan Aesthetics, which developed onabotulinumtoxinA, by injecting along the jawline and the vertical bands connecting the jaw and neck with one of the FDA-approved doses of the product based on severity, onabotulinumtoxinA temporarily reduces underlying muscle activity.
The company cited results from phase 3 clinical studies, which demonstrated statistical significance for the improvement in appearance of platysma bands from baseline with onabotulinumtoxinA compared with placebo on both investigator and patient assessment (P < .0001).
All secondary endpoints were also met, as measured by multiple validated, proprietary patient-reported outcome instruments. In two of the clinical studies, for example, 65% and 62% of patients reported being “very satisfied” or “satisfied,” respectively, with their neck and jawline definition 14 days after treatment with a dose of 26, 31, or 36 units of onabotulinumtoxinA, compared with 12% with placebo in both studies.
The development marks the fourth indication for onabotulinumtoxinA. The others are for moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity, moderate to severe lateral canthal lines associated with orbicularis oculi activity, and moderate to severe forehead lines associated with frontalis activity.
A version of this article appeared on Medscape.com.
Gotistobart Trial for NSCLC on Partial Clinical Hold
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
FDA OKs Novel Levodopa-Based Continuous Sub-Q Regimen for Parkinson’s Disease
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
FDA Approves Pfizer’s Hympavzi for Hemophilia A, B
The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.
“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release.
Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A.
The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors.
During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year.
Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi.
Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.
Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes.
Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April.
Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
A version of this article first appeared on Medscape.com.
The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.
“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release.
Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A.
The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors.
During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year.
Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi.
Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.
Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes.
Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April.
Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
A version of this article first appeared on Medscape.com.
The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.
“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release.
Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A.
The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors.
During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year.
Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi.
Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.
Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes.
Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April.
Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
A version of this article first appeared on Medscape.com.
FDA Panel Votes for Limits on Gastric, Esophageal Cancer Immunotherapy
During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher.
The agency usually follows the ODAC’s advice.
The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.
Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.
These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.
In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.
Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.
In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.
The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.
Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.
Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.
In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.
The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.
ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.
In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.
FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.
Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.
Still, one panelist said, it’s likely “the best dataset we will get.”
The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.
If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.
BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
A version of this article first appeared on Medscape.com.
During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher.
The agency usually follows the ODAC’s advice.
The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.
Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.
These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.
In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.
Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.
In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.
The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.
Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.
Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.
In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.
The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.
ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.
In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.
FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.
Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.
Still, one panelist said, it’s likely “the best dataset we will get.”
The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.
If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.
BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
A version of this article first appeared on Medscape.com.
During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher.
The agency usually follows the ODAC’s advice.
The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.
Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.
These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.
In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.
Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.
In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.
The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.
Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.
Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.
In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.
The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.
ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.
In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.
FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.
Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.
Still, one panelist said, it’s likely “the best dataset we will get.”
The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.
If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.
BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
A version of this article first appeared on Medscape.com.
FDA Okays Osimertinib After CRT in Locally Advanced, Unresectable NSCLC
Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.
The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
Trial Findings Supporting Latest Approval
AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.
The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
Adverse Events
Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
A version of this article first appeared on Medscape.com.
Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.
The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
Trial Findings Supporting Latest Approval
AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.
The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
Adverse Events
Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
A version of this article first appeared on Medscape.com.
Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.
The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
Trial Findings Supporting Latest Approval
AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.
The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
Adverse Events
Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
A version of this article first appeared on Medscape.com.
FDA Expands Indication for Amivantamab in Lung Cancer
Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News.
The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.
“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added.
The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.
The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48).
Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group.
The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.
The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.
A version of this article appeared on Medscape.com.
Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News.
The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.
“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added.
The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.
The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48).
Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group.
The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.
The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.
A version of this article appeared on Medscape.com.
Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).
The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News.
The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.
“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added.
The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.
The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48).
Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group.
The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.
The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.
A version of this article appeared on Medscape.com.
FDA OKs Adjuvant Ribociclib in Earlier Stage Breast Cancer
FDA also approved ribociclib and the aromatase inhibitor letrozole packaged together (Kisqali Femara Co-Pack, Novartis) for the same indication.
A rival cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib (Verzenio, Eli Lilly) carries a similar adjuvant indication, but use of this agent requires patients to be lymph node–positive.
There’s no such restriction for the new ribociclib indication, which “allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people,” lead investigator Dennis J. Slamon, MD, breast oncologist at the University of California Los Angeless, said in a Novartis press release.
The new indication joins ribociclib’s previous approval for advanced or metastatic HR-positive, HER2-negative breast cancer in combination with an aromatase inhibitor or fulvestrant.
The current approval was based on data from the NATALEE trial. NATALEE randomized 5101 patients with early-stage HR-positive, HER2-negative disease to either 400 mg ribociclib with an aromatase inhibitor or to an aromatase inhibitor alone following surgery.
Invasive disease-free survival at 36 months was 90.7% in the ribociclib arm vs 87.6% with aromatase inhibitor monotherapy (hazard ratio [HR], 0.749; P = .0006). The trial included patients with and without lymph node involvement.
At 4 years (well beyond NATALEE’s 3-year treatment window), the ribociclib group continued to do better, with an invasive disease-free survival rate of 88.5% vs 83.6% in the control arm.
Overall survival data remain immature but with a trend towards improved survival in the ribociclib arm (HR, 0.715; P < .0001), according to a recent report from the 2024 European Society for Medical Oncology Congress.
There were no new safety signals in the trial. Adverse events in the ribociclib group included neutropenia (62.5% overall; 44.3% grade 3/4), liver-related events (26.4% overall; 8.6% grade 3/4), QT prolongation (5.3% overall; 1.0% grade 3/4), and interstitial lung disease/pneumonitis (1.5% overall; 0.0% grade 3/4), according to Novartis.
Ribociclib dosing for the adjuvant indication is lower than for metastatic disease, but patients are on the same schedule — two 200 mg tablets once daily for 21 days followed by 7 days off in 28-day cycles. Treatment continues for 3 years.
Forty-two 200 mg tablets cost about $15,000, according to drugs.com. A patient assistance program is available through Novartis.
A version of this article appeared on Medscape.com.
FDA also approved ribociclib and the aromatase inhibitor letrozole packaged together (Kisqali Femara Co-Pack, Novartis) for the same indication.
A rival cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib (Verzenio, Eli Lilly) carries a similar adjuvant indication, but use of this agent requires patients to be lymph node–positive.
There’s no such restriction for the new ribociclib indication, which “allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people,” lead investigator Dennis J. Slamon, MD, breast oncologist at the University of California Los Angeless, said in a Novartis press release.
The new indication joins ribociclib’s previous approval for advanced or metastatic HR-positive, HER2-negative breast cancer in combination with an aromatase inhibitor or fulvestrant.
The current approval was based on data from the NATALEE trial. NATALEE randomized 5101 patients with early-stage HR-positive, HER2-negative disease to either 400 mg ribociclib with an aromatase inhibitor or to an aromatase inhibitor alone following surgery.
Invasive disease-free survival at 36 months was 90.7% in the ribociclib arm vs 87.6% with aromatase inhibitor monotherapy (hazard ratio [HR], 0.749; P = .0006). The trial included patients with and without lymph node involvement.
At 4 years (well beyond NATALEE’s 3-year treatment window), the ribociclib group continued to do better, with an invasive disease-free survival rate of 88.5% vs 83.6% in the control arm.
Overall survival data remain immature but with a trend towards improved survival in the ribociclib arm (HR, 0.715; P < .0001), according to a recent report from the 2024 European Society for Medical Oncology Congress.
There were no new safety signals in the trial. Adverse events in the ribociclib group included neutropenia (62.5% overall; 44.3% grade 3/4), liver-related events (26.4% overall; 8.6% grade 3/4), QT prolongation (5.3% overall; 1.0% grade 3/4), and interstitial lung disease/pneumonitis (1.5% overall; 0.0% grade 3/4), according to Novartis.
Ribociclib dosing for the adjuvant indication is lower than for metastatic disease, but patients are on the same schedule — two 200 mg tablets once daily for 21 days followed by 7 days off in 28-day cycles. Treatment continues for 3 years.
Forty-two 200 mg tablets cost about $15,000, according to drugs.com. A patient assistance program is available through Novartis.
A version of this article appeared on Medscape.com.
FDA also approved ribociclib and the aromatase inhibitor letrozole packaged together (Kisqali Femara Co-Pack, Novartis) for the same indication.
A rival cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib (Verzenio, Eli Lilly) carries a similar adjuvant indication, but use of this agent requires patients to be lymph node–positive.
There’s no such restriction for the new ribociclib indication, which “allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people,” lead investigator Dennis J. Slamon, MD, breast oncologist at the University of California Los Angeless, said in a Novartis press release.
The new indication joins ribociclib’s previous approval for advanced or metastatic HR-positive, HER2-negative breast cancer in combination with an aromatase inhibitor or fulvestrant.
The current approval was based on data from the NATALEE trial. NATALEE randomized 5101 patients with early-stage HR-positive, HER2-negative disease to either 400 mg ribociclib with an aromatase inhibitor or to an aromatase inhibitor alone following surgery.
Invasive disease-free survival at 36 months was 90.7% in the ribociclib arm vs 87.6% with aromatase inhibitor monotherapy (hazard ratio [HR], 0.749; P = .0006). The trial included patients with and without lymph node involvement.
At 4 years (well beyond NATALEE’s 3-year treatment window), the ribociclib group continued to do better, with an invasive disease-free survival rate of 88.5% vs 83.6% in the control arm.
Overall survival data remain immature but with a trend towards improved survival in the ribociclib arm (HR, 0.715; P < .0001), according to a recent report from the 2024 European Society for Medical Oncology Congress.
There were no new safety signals in the trial. Adverse events in the ribociclib group included neutropenia (62.5% overall; 44.3% grade 3/4), liver-related events (26.4% overall; 8.6% grade 3/4), QT prolongation (5.3% overall; 1.0% grade 3/4), and interstitial lung disease/pneumonitis (1.5% overall; 0.0% grade 3/4), according to Novartis.
Ribociclib dosing for the adjuvant indication is lower than for metastatic disease, but patients are on the same schedule — two 200 mg tablets once daily for 21 days followed by 7 days off in 28-day cycles. Treatment continues for 3 years.
Forty-two 200 mg tablets cost about $15,000, according to drugs.com. A patient assistance program is available through Novartis.
A version of this article appeared on Medscape.com.
Isatuximab Approved First-Line for Transplant-Ineligible MM
The new first-line indication joins two previous approvals of the CD38 antibody for later-line indications, one for relapsed disease with carfilzomib and dexamethasone, the other with pomalidomide and dexamethasone after at least two prior regimens that include lenalidomide and a proteasome inhibitor.
In addition to other MM indications, isatuximab’s anti-CD38 competitor on the US market, daratumumab (Darzalex — Johnson & Johnson), also carries a first-line indication for transplant-ineligible MM in combination with either lenalidomide and dexamethasone or bortezomib, melphalan, and prednisone.
Isatuximab’s new approval is based on the open-label IMROZ trial in 446 patients randomized 3:2 to either isatuximab or placebo on a background of bortezomib, lenalidomide, and dexamethasone.
At a median follow-up of 59.7 months, estimated progression-free survival (PFS) was 63.2% with isatuximab add-on vs 45.2% in the placebo arm. Median PFS was not reached in the isatuximab group but 54.3 months with placebo (hazard ratio, 0.60; 98.5% CI, 0.41-0.88; P < .001).
In a press release announcing the results, Sanofi said “IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody” to show benefit in combination with bortezomib, lenalidomide, and dexamethasone, the current standard of care for transplant-ineligible MM.
Upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 were the most common adverse events in the isatuximab arm of IMROZ, occurring in 20% or more of subjects.
Eleven percent of isatuximab patients died during treatment vs 5.5% in the placebo group, driven primarily by infections.
The recommended dose of isatuximab is 10 mg/kg every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity.
The cost is approximately $843 for 5 mL of the 20 mg/mL intravenous solution, according to Drugs.com.
A version of this article appeared on Medscape.com.
The new first-line indication joins two previous approvals of the CD38 antibody for later-line indications, one for relapsed disease with carfilzomib and dexamethasone, the other with pomalidomide and dexamethasone after at least two prior regimens that include lenalidomide and a proteasome inhibitor.
In addition to other MM indications, isatuximab’s anti-CD38 competitor on the US market, daratumumab (Darzalex — Johnson & Johnson), also carries a first-line indication for transplant-ineligible MM in combination with either lenalidomide and dexamethasone or bortezomib, melphalan, and prednisone.
Isatuximab’s new approval is based on the open-label IMROZ trial in 446 patients randomized 3:2 to either isatuximab or placebo on a background of bortezomib, lenalidomide, and dexamethasone.
At a median follow-up of 59.7 months, estimated progression-free survival (PFS) was 63.2% with isatuximab add-on vs 45.2% in the placebo arm. Median PFS was not reached in the isatuximab group but 54.3 months with placebo (hazard ratio, 0.60; 98.5% CI, 0.41-0.88; P < .001).
In a press release announcing the results, Sanofi said “IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody” to show benefit in combination with bortezomib, lenalidomide, and dexamethasone, the current standard of care for transplant-ineligible MM.
Upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 were the most common adverse events in the isatuximab arm of IMROZ, occurring in 20% or more of subjects.
Eleven percent of isatuximab patients died during treatment vs 5.5% in the placebo group, driven primarily by infections.
The recommended dose of isatuximab is 10 mg/kg every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity.
The cost is approximately $843 for 5 mL of the 20 mg/mL intravenous solution, according to Drugs.com.
A version of this article appeared on Medscape.com.
The new first-line indication joins two previous approvals of the CD38 antibody for later-line indications, one for relapsed disease with carfilzomib and dexamethasone, the other with pomalidomide and dexamethasone after at least two prior regimens that include lenalidomide and a proteasome inhibitor.
In addition to other MM indications, isatuximab’s anti-CD38 competitor on the US market, daratumumab (Darzalex — Johnson & Johnson), also carries a first-line indication for transplant-ineligible MM in combination with either lenalidomide and dexamethasone or bortezomib, melphalan, and prednisone.
Isatuximab’s new approval is based on the open-label IMROZ trial in 446 patients randomized 3:2 to either isatuximab or placebo on a background of bortezomib, lenalidomide, and dexamethasone.
At a median follow-up of 59.7 months, estimated progression-free survival (PFS) was 63.2% with isatuximab add-on vs 45.2% in the placebo arm. Median PFS was not reached in the isatuximab group but 54.3 months with placebo (hazard ratio, 0.60; 98.5% CI, 0.41-0.88; P < .001).
In a press release announcing the results, Sanofi said “IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody” to show benefit in combination with bortezomib, lenalidomide, and dexamethasone, the current standard of care for transplant-ineligible MM.
Upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 were the most common adverse events in the isatuximab arm of IMROZ, occurring in 20% or more of subjects.
Eleven percent of isatuximab patients died during treatment vs 5.5% in the placebo group, driven primarily by infections.
The recommended dose of isatuximab is 10 mg/kg every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity.
The cost is approximately $843 for 5 mL of the 20 mg/mL intravenous solution, according to Drugs.com.
A version of this article appeared on Medscape.com.
FDA Initiative Aims to Improve Diversity in Clinical Trials
NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.
This initiative, known as the according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.
Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
Lack of Trial Diversity Is Common Across Medicine
Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.
The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.
This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”
However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.
“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.
Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
Skin Color Is Inadequate to Define Race
When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.
The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.
If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.
“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.
The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.
Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.
The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.
Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.
Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.
Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.
A version of this article appeared on Medscape.com.
NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.
This initiative, known as the according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.
Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
Lack of Trial Diversity Is Common Across Medicine
Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.
The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.
This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”
However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.
“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.
Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
Skin Color Is Inadequate to Define Race
When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.
The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.
If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.
“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.
The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.
Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.
The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.
Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.
Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.
Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.
A version of this article appeared on Medscape.com.
NEW YORK — Underrepresentation by gender and race in major clinical trials has been a cause for complaint for decades, but the Food and Drug Administration (FDA) has drafted a regulatory solution to this issue expected to be implemented sometime in 2025.
This initiative, known as the according to Valerie M. Harvey, MD, MPH, associate clinical professor, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia. These rules will be codified, she said at the 2024 Skin of Color Update.
Once the DAP is enacted, “the sponsor must specify the rationale and goals for study enrollment by age, ethnicity, sex, and race,” she said. Furthermore, the submission to the FDA must “describe the methods to meet the diversity benchmarks.”
Lack of Trial Diversity Is Common Across Medicine
Although she focused on the relevance of this initiative to dermatology, Dr. Harvey said the lack of diversity in clinical trials is pervasive throughout medicine. In one survey of randomized controlled trials, less than 60% of trials even specified the race and ethnicity of the participants. In recent psoriasis trials, only 30% met a diversity definition of ≥ 20% of patients identifying as minority (Black, Hispanic, Asian, or other non-White group), said Dr. Harvey, who practices dermatology in Newport News, Virginia.
The FDA draft guidance for the DAP was released in June 2024 and is now available for submitting comments (until September 26). The plan is expected to be published in June 2025, according to Dr. Harvey. It will pertain to all pivotal and phase 3 trials enrolling 180 days after the publication date and will be relevant to all drugs and biologics as well as certain devices.
This initiative could be a critical step toward ensuring diversity in major clinical trials after years of stagnation, Dr. Harvey said, noting that despite repeated calls for more diversity in clinical trials, the literature suggests “little progress.”
However, she said that increasing diversity in clinical trials is just one step toward gathering data about the generalizability of efficacy and safety across racial and ethnic groups. A much more complex issue involves how race and ethnicity are defined in order to understand differences, if any, for efficacy and risk.
“Race is a dynamic social construct and a poor measure for biologic variation and skin color,” Dr. Harvey said. This means that work is needed to address the more complex issue of race and ethnicity stratification that will help clinicians understand the relative benefits and risks for the drugs in these trials.
Rather than differences based on genetic or other sources of biologic differences, she said, outcomes by race alone are often suspected of reflecting disparities in access to healthcare rather than a difference in therapeutic response.
Skin Color Is Inadequate to Define Race
When stratifying patients by race or ethnicity, Dr. Harvey said that “we have to be very, very careful in considering the study purpose and what the study question is.” A study attempting to compare benefits and risks among subgroups by race or ethnicity will require descriptors beyond skin color.
The recognized limitations of measuring skin tone as a surrogate of race are one reason for widespread interest in moving away from the Fitzpatrick skin type (FST) rating that has been widely considered a standard, according to Dr. Harvey. Several alternatives have been proposed, including the Monk Skin Tone Scale, the Individual Typology Angle, and the Eumelanin Human Skin Color Scale, but she cautioned that these are less well validated and generally have the limitations of the FST.
If skin color was ever useful for grouping individuals on the basis of shared physiology, growing rates of intermarriage and immigration have made skin color increasingly irrelevant to racial identity. If the goal is to evaluate the safety and efficacy of drugs across racial groups and ethnicities, the characterization of populations will almost certainly require multiple descriptors and biomarkers, she said.
“It is very important to have many tools for characterizing patients by skin type,” Susan Taylor, MD, professor of dermatology and vice chair for diversity, equity, and inclusion for the Department of Dermatology, University of Pennsylvania, Philadelphia, said in an interview at the meeting.
The reason is “there are limitations to all of them,” she said, noting also that the questions being asked about how and if skin color and race are relevant to therapeutic options differ by the question, such as innate response or access to care.
Dr. Taylor is part of a workshop that she said is evaluating a combination of instruments for characterizing skin color and race in ways relevant to the specific question being asked.
The solutions might differ. While simple clinical assessments involving skin color might be made with methods captured on a smartphone app, Dr. Taylor acknowledged that far more complex tools might be required to document the effect of racial or ethnic differences in drug efficacy and safety in a research setting.
Outside of a research setting, any tools that might be useful for assessing race as a variable must be practical, according to Dr. Harvey. She suggested that these must be time efficient, of reasonable cost, and most importantly, reliable.
Tools meeting these criteria do not currently exist, but Dr. Harvey said the work is underway. She expects a “top-down” collaborative approach to validate alternatives to the FST. If such tools can be developed with buy-in from the FDA, they might be particularly useful for translating trial data to patient care, she added.
Dr. Harvey reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Johnson & Johnson, L’Oréal, and SkinCeuticals. Dr. Taylor, president-elect of the American Academy of Dermatology, reported financial relationships with more than 25 pharmaceutical and cosmetic companies.
A version of this article appeared on Medscape.com.
FROM SOC 2024