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FDA Approves Bispecific HER2 Antibody for Biliary Tract Cancer
This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication.
Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.
The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.
Zanidatamab Trial Results
The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.
The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.
The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals.
Boxed Warning and Adverse Events
The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.
The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity.
Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.
An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.
A version of this article appeared on Medscape.com.
This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication.
Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.
The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.
Zanidatamab Trial Results
The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.
The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.
The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals.
Boxed Warning and Adverse Events
The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.
The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity.
Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.
An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.
A version of this article appeared on Medscape.com.
This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication.
Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.
The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.
Zanidatamab Trial Results
The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.
The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.
The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals.
Boxed Warning and Adverse Events
The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.
The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity.
Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.
An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.
A version of this article appeared on Medscape.com.
New Cause of Sexually Transmitted Fungal Infection Reported in MSM
A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.
“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.
“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.
The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.
All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.
Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.
Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.”
Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.
“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.”
Encourage Reporting and Identify New Infections
“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.
“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.
In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.”
Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.
The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”
“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.
Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.”
Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.
The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.
“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.
“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.
The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.
All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.
Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.
Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.”
Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.
“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.”
Encourage Reporting and Identify New Infections
“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.
“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.
In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.”
Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.
The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”
“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.
Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.”
Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.
The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.
“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.
“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.
The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.
All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.
Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.
Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.”
Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.
“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.”
Encourage Reporting and Identify New Infections
“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.
“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.
In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.”
Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.
The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”
“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.
Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.”
Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.
The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
FROM THE MMWR
Duloxetine Bottles Recalled by FDA Because of Potential Carcinogen
The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.
Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.
The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.
Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.
“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.
The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.
The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.
The recall was initiated on October 10 and is ongoing.
“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”
The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”
Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.
The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.
Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.
The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.
Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.
“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.
The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.
The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.
The recall was initiated on October 10 and is ongoing.
“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”
The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”
Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.
The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.
Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.
The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.
Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.
“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.
The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.
The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.
The recall was initiated on October 10 and is ongoing.
“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”
The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”
Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.
The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
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.
Tirzepatide Shortage Resolved? FDA Says Yes, Compounders No
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
FDA OKs Next-Gen Cologuard Test for CRC Screening
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
FDA Approves Ustekinumab Biosimilar Otulfi
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
A version of this article first appeared on Medscape.com.
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
A version of this article first appeared on Medscape.com.
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
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.
Bimekizumab Gains FDA Approval for Psoriatic Arthritis, Axial Spondyloarthritis
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx; UCB) for adult patients with active psoriatic arthritis (PsA), active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS).
The drug, an interleukin (IL)–17A and IL-17F inhibitor, was first approved in October 2023 for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
“In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the US have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to 2 years,” said Emmanuel Caeymaex, executive vice president, head of patient impact, and chief commercial officer of UCB in a press release.
The recommended dosage of bimekizumab for adult patients with active PsA, nr-axSpA, or AS is 160 mg by subcutaneous injection every 4 weeks. For patients with PsA and coexistent moderate to severe plaque psoriasis, the dosage is the same as for patients with plaque psoriasis. The dosing for plaque psoriasis is to administer 320 mg (two 160-mg injections) by subcutaneous injection at weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16.
PsA Clinical Trials
The approval for PsA was based on data from two phase 3 clinical trials, including 852 participants naive to biologics (BE OPTIMAL) and 400 participants with inadequate response to treatment with one or two tumor necrosis factor (TNF) inhibitors (BE COMPLETE). Both studies met their primary endpoint, 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, as well as ranked secondary endpoints. Secondary endpoints included minimal disease activity (MDA) and Psoriasis Area and Severity Index 100 (complete skin clearance) at week 16.
At 16 weeks:
- About 44% of both the biologic-naive (189 of 431) and TNF inhibitor–resistant (116 of 267) groups receiving bimekizumab achieved ACR50 response, compared with 10% (28 of 281) and 7% (9 of 133) receiving placebo, respectively.
- About 45% of all patients treated with bimekizumab achieved MDA.
- Nearly 60% of TNF inhibitor–resistant patients had complete skin clearance.
These responses generally were sustained for 1 year. The most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection.
NR-axSpA and AS Clinical Trials
The approval for active nr-axSpA and active AS was based on data from two clinical studies, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Both studies met their primary endpoint, 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks.
Key findings included:
- In nr-axSpA patients, 47.7% (61 of 128) receiving bimekizumab achieved ASAS40 at week 16, compared with 21.4% (27 of 126) receiving placebo.
- In AS patients, 44.8% (99 of 221) in the bimekizumab group achieved ASAS40 response at week 16 vs 22.5% (25 of 111) receiving placebo.
- At 1 year in both groups, 60% treated with bimekizumab achieved an Ankylosing Spondylitis Disease Activity Score < 2.1.
In nr-axSpA, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsillitis, increase in transaminase, and urinary tract infection. In AS, the most common adverse reactions are upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection-site pain, rash, and vulvovaginal mycotic infection.
Bimekizumab was approved by the European Commission for the same rheumatologic indications in June 2023.
Bimekizumab is currently available to eligible patients in the United States, according to the press release.
A version of this article first appeared on Medscape.com.