FDA Action Alert: Catalyst, GSK, BMS and more

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace

The FDA is welcoming June with four action events scheduled over the next two weeks, including one to expand the patient pool for a respiratory syncytial virus vaccine. The agency will also hold two major advisory committee meetings.

Read below to learn more.

Catalyst aims for higher maximum daily dose for rare disease drug

By June 4, the FDA is expected to issue its opinion on Catalyst Pharmaceuticals’ supplemental new drug application (sNDA), which proposes a higher maximum daily dose of the potassium channel blocker Firdapse (amifampridine) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS).

LEMS is a rare neuromuscular disorder characterized by an autoimmune disorder in which antibodies attack the patient’s own calcium channels. LEMS is a rare neuromuscular disorder that presents as weakness in the limbs. LEMS is also often associated with an underlying cancer, most commonly small cell lung cancer. In some patients, LEMS manifests as the first sign of these cancers.

According to its name, the exact mechanism by which Firdapse treats LEMS is still unknown.

The FDA first approved Firdapse in November 2018 based on two Phase III trials that showed the drug could produce significantly greater improvements in muscle strength and physical well-being than a placebo. The most common side effects of Firdapse include tingling, upper respiratory tract infections, and abdominal pain. The drug’s approval was expanded to include pediatric patients in 2022.

Currently, Firdapse can be administered at a maximum daily dose of 80 mg. With its sNDA, which the FDA accepted in October 2023, Catalyst hopes to increase this limit to 100 mg.

Lykos Therapeutics’ MDMA-assisted PTSD therapy faces trial

On June 4, the FDA’s Psychopharmacologic Drugs Advisory Committee will meet to discuss Lykos Therapeutics’ MDMA-assisted therapy for post-traumatic stress disorder.

CEO Amy Emerson said in May 2024 that Lykos’ application will be the “first MDMA-assisted therapy and psychedelic-assisted therapy to be reviewed by the Psychopharmacologic Drugs Advisory Committee,” adding that the meeting itself was a “significant milestone in the field of psychedelic medicine.”

Lykos proposes using MDMA tablets in conjunction with psychotherapy and supportive mental health interventions for PTSD. The biotechnology company bases its application on data from the Phase III MAPP1 and MAPP2 trials, which showed significant improvements in patient scores on the Clinician-Administered PTSD Scale for DSM-5, the current gold standard in PTSD symptom assessment.

Last month, however, the Institute for Clinical and Economic Review (ICER) pointed out anomalies in Lykos’ study design, suggesting that therapists and patients recruited for the study already had “very strong biases” against MDMA, which may have distorted documentation of treatment success.

ICER also found that some participants were pressured to keep the results of Lykos’ trials “positive.” In addition, because of MDMA’s psychedelic effects, almost all patients receiving the active treatment were able to identify their allocation, making the trial “essentially unblinded.”

GSK considers expanded label for RSV vaccine

GSK proposes using its Arexvy vaccine against respiratory syncytial virus (RSV) to vaccinate people aged 50 to 59 who are at increased risk of infection. The FDA’s decision is expected on June 7.

If approved, Arexvy would be the first RSV vaccine to protect this age group from the virus, helping GSK maintain its lead in the RSV race.

Arexvy became the first FDA-approved RSV vaccine in May 2023 and is currently approved for use in adults ages 60 and older. The vaccine has since become the RSV market leader. In its third-quarter 2023 report, GSK announced that Arexvy accounted for more than 60% of RSV vaccines sold at retail in the U.S. and generated nearly $860 million in its first full commercial quarter.

GSK is supporting Arexvy’s supplemental Biologics License Application (sBLA) with a Phase III study evaluating the vaccine’s immune response and safety in a younger elderly population. The pharmaceutical company published initial data from this study in October 2023, showing that the vaccine could elicit an immune response in people in their 50s that was non-inferior to that seen in its currently approved patient population.

Aside from immunogenicity, the late-stage study also found that Arexvy’s safety and reactogenicity profiles were consistent with those seen in previous studies. The most common side effects were headache, pain and fatigue.

Ipsen and Genfit propose elafibranor for the treatment of primary biliary cholangitis

The FDA has until June 10 to decide on Ipsen and Genfit’s NDA for their dual peroxisome-activated receptor alpha/delta (PPAR α,δ) agonist elafibranor for the treatment of primary biliary cholangitis (PBC).

If approved, elafibranor could “transform the treatment of this difficult disease … and provide a new second-line treatment option where few effective options currently exist,” said Christelle Huguet, head of research and development at Ipsen, in a statement accepting the NDA. The FDA has granted elafibranor priority review.

PBC is a rare autoimmune disease of the liver characterized by the progressive destruction of the bile ducts, which in turn impairs the body’s ability to eliminate toxins. Patients with PBC typically experience fatigue and itching and eventually develop cirrhosis of the liver. If left untreated, PBC can also lead to liver failure and death.

Elafibranor is an orally available small molecule drug candidate that boosts lipid metabolism. Elafibranor may also reduce inflammation, fibrosis and steatosis, all of which are hallmarks of PBC. It was originally developed for nonalcoholic steatohepatitis, but those plans were scrapped due to disappointing Phase III data.

In November 2023, Ipsen and Genfit published data from the Phase III ELATE trial showing that the drug candidate can induce high biochemical response rates in PBC patients. Elafibranor also normalized alkaline phosphatase levels in a subset of treated patients.

FDA’s PCNS Adcomm meets to discuss Lilly’s donanemab

On June 10, the FDA will convene its Peripheral and Central Nervous System Drugs Advisory Committee to discuss Eli Lilly’s application for its anti-amyloid antibody donanemab to treat Alzheimer’s disease.

According to a March 2024 announcement, the panel of external experts will focus on the “unique study design” of Lilly’s TRAILBLAZER-ALZ 2 trial and the potential impact of that design on the trial’s efficacy results.

In TRAILBLAZER ALZ-2, Lilly enrolled more than 1,700 patients with early-stage Alzheimer’s disease diagnosed through cognitive screening and brain scans. The study’s treatment protocol was unique in that it allowed patients to stop donanemab treatment after amyloid clumps in their brains fell below a predefined level.

This novel study design may have cost donanemab accelerated approval, which the FDA rejected in January 2023. At the time, the regulator noted that it needed to see data from at least 100 patients who had been treated with donanemab for 12 or more consecutive months.

The meeting on donanemab comes as the FDA considers eliminating the adcomm vote altogether and instead favoring a “broader discussion” of the issues surrounding the product in question, Commissioner Robert Califf said during the 2023 Biopharma Congress meeting.

BMS awaits FDA ruling on Agutyro in NTRK-positive solid tumors

Bristol Myers Squibb is seeking an extension of the approval for its tyrosine kinase inhibitor Augtyro (repotrectinib). The pharmaceutical company wants to use the drug in patients aged 12 years and older with locally advanced or metastatic solid tumors that carry the neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The FDA has set June 15 as the target date.

In its sNDA, which the FDA accepted and granted priority review in February 2024, BMS presented data from the Phase I/II TRIDENT-1 trial showing that Augtyro can induce “clinically meaningful responses” in patients. The response was durable, even in patients with common resistance mutations.

The pharmaceutical company also presented results from the CARE study, which complemented TRIDENT-1 with promising data from pediatric patients and young adults whose tumors had ALK, ROS1 or NTRK mutations.

Augtyro is an oral drug that blocks the proto-oncogene ROS1 as well as various tyrosine kinases. According to its name, Augtyro’s mechanism of action blocks fusion proteins containing ROS1 domains that would otherwise trigger signaling cascades that culminate in the uncontrolled proliferation of cancer cells.

Augtyro was first approved in November 2023 to treat patients with advanced or metastatic non-small cell lung cancer who tested positive for ROS1.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Contact him on LinkedIn or email him at [email protected] or [email protected].