FDA/CDC

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

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

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine

All infants and children perinatally exposed to the hepatitis C virus (HCV) should be tested and, if necessary, treated, according to new guidance from the Centers for Disease Control and Prevention.

In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.

HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).

About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.

This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
 

The new recommendations

• Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
• Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
• Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.

“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
 

A growing problem

The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.

Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.

The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.

Northwell Health

Northwestern Medicine

Northwestern Medicine

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.

Olivier Le Moal/Getty Images

“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.

The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.

The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.

Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.

Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.

Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.

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

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The Food and Drug Administration has approved mirikizumab-mrkz (Omvoh, Eli Lilly) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

Mirikizumab is a humanized monoclonal antibody that targets the p19 subunit of IL-23, a key player in UC-related inflammation. It’s the first IL-23 inhibitor to be approved in the United States for UC. The drug is administered intravenously.

The approval of mirikizumab represents a “novel scientific advancement, providing a treatment that may offer relief from three key symptoms – stool frequency, rectal bleeding, and bowel urgency – regardless of past biologic use,” Bruce Sands, MD, chief of the division of gastroenterology, Icahn School of Medicine at Mount Sinai, who worked on the pivotal trials, said in a news release.

Last April, the FDA withheld approval of the drug, citing issues related to the proposed manufacturing of the drug. The agency did not express concerns about safety or efficacy data, Eli Lilly confirmed.

The FDA approval was based on results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials, published in the New England Journal of Medicine.

All patients in the LUCENT program had moderately to severely active UC and had experienced treatment failure or could not tolerate past treatments, including biologic therapies.

The induction trial enrolled 1,281 patients; 544 patients who had a response to mirikizumab were enrolled in the maintenance phase.

The trials showed that mirikizumab achieved primary and secondary endpoints, including sustained clinical remission and significantly improved bowel urgency.

“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer of the Crohn’s and Colitis Foundation, said in the news release.

Mirikizumab offers “new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency–related accidents and other symptoms associated with ulcerative colitis,” Mr. Osso added.

The most common adverse reactions associated with mirikizumab were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

The drug label contains warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations.

A version of this article was originally published on Medscape.com .

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

The U.S. Food and Drug Administration has approved tablets of ivosidenib (Tibsovo, Servier Pharmaceuticals) for adults with isocitrate dehydrogenase (IDH)-1 mutated relapsed or refractory myelodysplastic syndromes.

The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.

Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.

Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.

The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.

Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.

Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.

Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.

Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.

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

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com