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The FDA has approved UCB's Bimzelx for moderate-to-severe hidradenitis suppurativa, offering a new treatment option for this painful autoimmune skin disease.

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Syndax Pharmaceuticals recently announced the FDA approval of Revuforj (revumenib) for the treatment of relapsed or refractory acute leukemia in adult and pediatric patients one year and older. It is indicated for patients with a lysine methyltransferase 2A gene (KMT2A) translocation, according to a 

Onco360 was chosen as a specialty pharmacy partner by Syndax, a seperate 

“Today marks another major milestone in the leukemia community,” Michael Metzger, CEO and director of Syndax said during the investor call. “With the FDA approval in hand, we look forward to launching Revuforj in the United States this month.”

Revuforj is the first and only menin inhibitor approved by the FDA. It works by preventing rearrangements in KMT2A gene, which can lead to the development of leukemia cells. An estimated 95% ofKMT2Ar acute leukemia patients have KMT2A translocation. This abnormality is seen in about 10% of all leukemias.

Only about 5% of patients with this mutation achieve complete remission with current third-line treatment with a median overall survival rate of less than three months, according to the news release. More than half of patients will relapse after first-line treatment.

The approval of Revuforj is based on positive data from the AUGMENT-101 clinical trial in which 21% of patients reached complete remission with partial hematological recovery, meaning that although no was cancer detected, blood cell counts have not fully recovered. This took about six months.

Safety evaluation of Revuforj was based on an analysis of 135 patients. Serious adverse reactions were seen in 73% of patients and 3% of patients died. Two patients died from differentiation syndrome, one hemorrhaged and another “died suddenly,” the news release reports. Differentiation syndrome is a side effect of certain blood cancer drugs that can present as trouble breathing, fever and weight gain. It is fatal within the first few weeks of treatment. 

The most common serious adverse reactions were infection (24%), febrile neutropenia (19%) and bacterial infection (17%). The most common adverse reactions were hemorrhage (53%), nausea (51%) and increased phosphate (50%). As a result, dose interruptions occurred in 42% of patients.

Revuforj will be available as 110 mg and 160 mg tablets to be taken twice daily, depending on weight. It’s expected to be available via specialty pharmacies later this month. There will also be a 25 mg tablet option for patients who weigh less than 40 kg, expected late in the first quarter or early second quarter of 2025. Until then, an oral solution will be available through an expanded access program. The wholesale acquisition price is $39,500 for a 30-day supply of the 110 or 160 mg tablets, according to the investor call.  

Syndax will eventually offer financial assistance via SyndAccess, a newly established support and resource program for patients. 

The FDA previously granted Revuforj Breakthrough Therapy, Fast Track and Priority Review designations. A New Drug Application was granted through FDA's Real Time Oncology Review program.

Relapsed or refractory acute leukemia with a KMT2A translocation currently has an overall survival rate of less than one year when treated with frontline therapies. 

Formulary Watch

Clinical

FDA Approves First-in-Class Drug for Rare Leukemia 

The American Lung Association (ALA) is hoping to lower rates of undiagnosed pulmonary arterial hypertension (PAH) through a new 

The new campaign is a response to the persistent problem of delayed diagnosis among people with PAH, but it also reflects growing attention to the disease by drug developers and scientific investigators.

Left untreated, PAH can be deadly. However, therapy can significantly improve symptoms and extend patient survival. The most recent therapeutic advancement was the FDA’s approval of Winrevair (sotatercept) earlier this year. Merck & Co.’s drug is an activin signaling inhibitor therapy, the first of its kind.

The development of Winrevair was part of a wave of new research clarifying the pathogenesis of the disease and identifying potential new drug targets. Yet, that wave of scientific interest in the disease has not necessarily translated into greater public awareness of the disease.

Harold Wimmer, M.S., the ALA’s president and CEO, said the goal of the campaign is to improve the lives of people with the disease by helping them get earlier access to therapy.

“Through this campaign, we hope to improve awareness and understanding of PAH, promote early diagnosis, and provide valuable resources for patients and caregivers,” he said, in a press release.

The campaign is being supported by Merck, which reported sales of $149 million for Winrevair as of the third quarter of 2024. The company noted that Winrevair was also recently approved in Europe, and has already launched in Germany. Merck said it expects to obtain reimbursement for the drug in most of the other major European markets in the second half of next year.

The ALA estimates that between 500 and 1,000 people are diagnosed with PAH each year in the United States, though it is unknown how many people have undiagnosed cases. Historically, late diagnosis of PAH has been a significant challenge.

 found that the mean time from symptom onset to diagnosis was 47 months among patients with idiopathic PAH. On average, patients reported seeing their primary care doctor 5.3 times and a specialist 3 times before being seen at a PAH center.

 found that 1 in 5 adult patients in a PAH registry had reported symptoms for more than 2 years before their disease was correctly diagnosed as PAH. The authors of that study found that younger age and a history of common respiratory disorders were associated with delays in PAH diagnosis.

In the early stages of the disease, symptoms may be fewer or non-apparent to patients. When the disease progresses, symptoms of the disease can include shortness of breath, fatigue, swelling of the feet and legs, dizziness, chest pain, and heart palpitations. The ALA noted that asthma and congestive heart failure both have similar symptoms to PAH, which can lead to misdiagnosis in some patients.

Patients with pulmonary arterial hypertension often experienced delays in obtaining a correct diagnosis.

Lung Association, Merck Partner to Raise Awareness of PAH

The FDA will convene a meeting of the Psychopharmacologic Drugs Advisory Committee on June 4, 2024, to review data for midomafetamine to treat patients with post-traumatic stress disorder (PTSD). PTSD is a mental health condition affecting about 13 million Americans each year, yet currently available treatments provide only modest efficacy; there are high treatment discontinuation rates.

Developed by Lykos Therapeutics, midomafetamine is 3,4-methylenedioxymethamphetamine (MDMA) — commonly known as ecstasy — a class of psychoactive compounds. The FDA’s target action date is Aug. 11, 2024. If approved, this would be the first psychedelic-assisted therapy for post-traumatic stress disorder.

“This will be the first MDMA-assisted therapy and psychedelic-assisted therapy to be reviewed by the Psychopharmacologic Drugs Advisory Committee, a significant milestone in the field of psychedelic medicine, resulting from decades of clinical research and advocacy,” Amy Emerson, CEO of Lykos Therapeutics, said in a 

IPD Analytics LLC predicts the wholesale acquisition cost will be between $5,000 and $10,000 per drug course and the drug will be administered by physicians.

The committee will discuss the overall benefit-risk profile of the product, including the potential public health impact. Committtee members will review results from two phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA. 

 and MAPP2 both met the primary endpoint as measured by the change from baseline in Clinician-Administered PTSD Scale for DSM-5 and the key secondary endpoint of improvement in functional impairment associated with PTSD.

 in September 2023. In the trial, 45 of 52 (86.5%) patients treated with midomafetamine achieved a clinically meaningful benefit, and 37 of 52 (71.2%) patients no longer met criteria for PTSD by study end.

In both trials, treatment was not significantly affected by disease severity, risk of hazardous alcohol or substance use disorder, severe adverse childhood experiences or dissociative subtype. Both studies had a low drop out rate: 1.9% for the those treated with midomafetamine in MAPP2.

No serious adverse events were reported in the MDMA group in both studies. Common treatment-related adverse events included mild increases in blood pressure and pulse. Midomafetamine did not appear to increase the risk of suicidal ideation.

In January 2024, a new reimbursement code went into affect for psychedelic therapies. The American Medical Association 

 in May 2023 a Current Procedural Terminology (CPT) III code for psychedelic therapies.

Midomafetamine is also being studied in patients with PTSD in Europe. Lykos recently announced that it had 

 a phase 2 study (MP18) in Europe. The study included 21 patients treated in sites in the Netherlands, United Kingdom, Czech Republic, Germany, and Norway. The study included an optional fMRI sub-study assessing changes in brain activity in subjects with PTSD.

“There is an urgent need for new and effective evidence-based treatments for PTSD in Europe where the reported PTSD prevalence is up to 6.7%,” Eric Vermetten, M.D., Ph.D., professor of psychiatry at Leiden University Medical Center and lead investigator of the study, said in a news release.

If approved, midomafetamine would be the first psychedelic-assisted therapy approved for any mental health condition. The advisory committee meeting is June 4, 2024.

FDA Sets Date for Advisory Committee Meeting for Midomafetamine for PTSD

The FDA’s Psychopharmacologic Drugs Advisory Committee yesterday 

 recommending Lykos Therapeutics’ midomafetamine to treat patients with post-traumatic stress disorder (PTSD).

Advisory committee members voted 2 for and 9 against on whether the available data show that midomafetamine is effective in patients with PTSD. They also voted 1 yes to 10 no on the question of whether the benefits of midomafetamine with FDA's proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD.

“We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved,” Amy Emerson, CEO of Lykos Therapeutics, said in a 

. “We are grateful to the advocates, clinical trial participants and people living with PTSD who shared their testimony in the open public hearing and through written comments, and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD.”

PTSD is a mental health condition affecting about 13 million Americans each year, yet currently available treatments provide only modest efficacy; there are high treatment discontinuation rates.

Midomafetamine is 3,4-methylenedioxymethamphetamine (MDMA) — commonly known as ecstasy — a class of psychoactive compounds. The FDA’s target action date is Aug. 11, 2024.

Committee members reviewed results from two phase 3 studies evaluating the efficacy and safety of MDMA. Both 

In MAPP1 67% of patients with severe PTSD receiving MDMA-assisted therapy no longer met the criteria for PTSD after 18 weeks of study treatment. In the MAPP2 study, 71% of patients with moderate to severe PTSD no longer met the criteria for PTSD after 18 weeks of MDMA-assisted therapy. Results from 

Adverse effects in both trials were mild to moderate and did not include increased suicidal thoughts or actions.

 ahead of the meeting, FDA officials expressed several concerns. First was the issue of whether trials of midomafetamine could be blinded, which may impact the efficacy results. Because of the alternations in mood and cognition caused by midomafetamine, the majority of patients in both the treatment arm and placebo arm were able to guess which treatment they received. “Participants experienced functional unblinding due to the effects of the drug itself. Functional unblinding can introduce bias in clinical studies,” regulators said.

Although Lykos conducted a follow up of patients six months to two years after the initial study period, about 25% of patients dropped out before the follow-up visit. Additionally, some patients had used other therapies before the follow-up visit.

FDA officials were also concerned about the safety results, saying in the briefing document that the cardiac safety results were not well characterized. Additionally, liver function studies were only done in the phase 1 and phase 2 studies and not in the phase 3 trials. Liver injury has been identified in the literature reports from illicit use of MDMA.

The committee members who voted no on the question of whether the available data show that midomafetamine is effective expressed concerns about the functional unblinding and whether that impacted efficacy.

“I felt the functional unblinding, the lack of management for expectation bias and also selection bias and not incorporating that into some kind of statistical model is meaningless,” chairman Rajesh Narendran, M.D., attending psychiatrist, resolve Crisis Services, at UPMC Western Psychiatric Hospital in Pittsburgh, said after the vote

Of committee members who voted yes on the same question was Walter S. Dunn, M.D., Ph.D., assistant clinical professor at the University of California Los Angeles, Department of Psychiatry.

“I think there are concerns about the functional unblinding in addition to the expectation bias, potentially reducing my confidence and the effect sizes that were reported,” he said. “However, I can’t overlook the fact that the effect sizes were fairly large. This treatment plus psychotherapy can be effective for post-traumatic stress disorder.”

Martin R. Steele, cofounder of Reason for Hope and founder & President of the Veteran Mental Health Leadership Coalition, said in a statement that committee lost sight of the bigger picture. "We lose 17 to 44 Veterans every single day to deaths of despair such as suicide or overdose – often resulting from unresolved trauma in service to this country – and the problem only seems to be getting worse. Despite rates of PTSD and suicide increasing for decades, we have seen little progress with new treatments, including no new FDA approved drugs for PTSD in over 20 years."

He said the benefits of MDMA, particularly alongside a stringent REMS,  outweigh the risks. "Considering the clear limitations of currently available medications such as SSRIs and talk therapies, MDMA-AT offers a seemingly obvious and logical approach to treating PTSD. The drug’s ability to rapidly establish therapeutic rapport and reduce fear response makes it easier to commit to and engage in a psychotherapeutic process that involves confronting often highly traumatic memories."

This story was updated to include comment from Martin Steele.

Patients with PTSD in the clinical trials of midomafetamine were able to guess whether they received treatment or placebo. Regulators and advisory committee members said this could have impacted efficacy results. FDA’s decision is expected by Aug. 11, 2024.



Updated: FDA Committee, Concerned about Bias, Votes No on Psychedelic in PTSD

This is an excerpt of a story that first appeared on American Journal of Managed Care.

The FDA has issued a complete response letter (CRL) for midomafetamine capsules (MDMA) in combination with assisted therapy for adults living with 

Upon completion of its review, the FDA stated that it could not approve the treatment based on the data submitted and suggested Lykos Therapeutics conduct an additional phase 3 study to expand on the efficacy and safety profile.

Lykos Therapeutics is planning to meet with the FDA to request "reconsideration of the decision and to further discuss the agency's recommendations for a resubmission seeking regulatory approval for midomafetamine capsules," according to the 

In June, an FDA advisory committee voted against approval of midomafetamine capsules (MDMA) for adults living with posttraumatic stress disorder (PTSD).


Calum Yacoubian, M.D.

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