FDA Action Alert: Lykos, GSK, BMS and More

Pictured: A scientist with pill bottles in front o

Pictured: A scientist with pill bottles in front o

In the next two weeks, the FDA is scheduled to decide on four drug applications and hold two highly anticipated advisory committee meetings.

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

The FDA is welcoming June with four target action dates in the coming two weeks, including one to expand the patient pool for a respiratory syncytial virus vaccine. The regulator will also hold two big advisory committee meetings.

Read below for more.

Lykos Therapeutics’ MDMA-Assisted PTSD Therapy Faces Adcomm

On June 4, the FDA’s Psychopharmacologic Drugs Advisory Committee will convene 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 is a “significant milestone in the field of psychedelic medicine.”

Lykos is proposing to use MDMA tablets in conjunction with psychotherapy and supportive mental health interventions for PTSD. The biotech is backing its application with data from the Phase III MAPP1 and MAPP2 studies, which showed significant improvements in patients’ scores in the Clinician-Administered PTSD Scale for DSM-5, currently the gold standard in PTSD symptom evaluation.

Last month, however, the Institute for Clinical and Economic Review (ICER) flagged anomalies in Lykos’ study design, pointing out that therapists and patients recruited into the study already held “very strong prior beliefs” about MDMA, which could have skewed the documentation of treatment benefits.

ICER also noted that some participants were pressured to keep the results of Lykos’ studies “favorable.” Moreover, due to the psychedelic effects of MDMA, nearly all patients who received the active treatment could identify their assignment, making the study “essentially, unblinded.”

GSK Eyes Expanded Label for RSV Vaccine

GSK is proposing to use its respiratory syncytial virus (RSV) vaccine Arexvy to inoculate people aged 50 to 59 who are at an increased risk of the infection. The FDA’s decision is due on June 7.

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

Arexvy became the first FDA-approved RSV vaccine in May 2023, and is currently authorized for use in adults aged 60 years and above. The vaccine has since become the RSV market leader. In its third-quarter 2023 report, GSK revealed that Arexvy had captured more than 60% of retail RSV vaccinations in the U.S. and brought in nearly $860 million in its first full commercial quarter.

GSK is backing Arexvy’s supplemental Biologics License Application (sBLA) with a Phase III study that looked at the immune response and safety of the vaccine in a younger senior population. The pharma unveiled early data from this trial in October 2023, showing that the shot could elicit an immune response in people in their 50s that was non-inferior to that 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 what had been determined in prior trials. The most common side effects were headache, pain and fatigue.

Ipsen, Genfit Propose Elafibranor for 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 “change the management of this challenging condition . . . offering a new second-line treatment choice, where the number of effective options are currently limited,” Christelle Huguet, head of R&D at Ipsen, said in a statement announcing the NDA’s acceptance. The FDA has granted elafibranor priority review.

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

Elafibranor is an orally available small molecule drug candidate that works by boosting lipid metabolism. Elafibranor can also reduce inflammation, fibrosis and steatosis, all of which are hallmarks of PBC. It was originally being 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 demonstrating that the drug candidate can elicit high rates of biochemical response in PBC patients. Elafibranor also normalized alkaline phosphatase levels in a subset of treated patients.

FDA’s PCNS Adcomm Convenes 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 for the treatment of Alzheimer’s disease.

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

In TRAILBLAZER ALZ-2, Lilly enrolled more than 1,700 patients with early symptomatic Alzheimer’s disease, as diagnosed with cognitive screening and brain scans. The trial’s treatment protocol was unique in that it allowed patients to stop donanemab treatment after amyloid clumps in their brains had dropped below a pre-defined level.

This novel trial 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 donanemab meeting comes as the FDA mulls eliminating the adcomm vote entirely, instead favoring a “more comprehensive discussion” regarding the issues surrounding the product in question, Commissioner Robert Califf said during the 2023 Biopharma Congress meeting.

BMS Awaits FDA Verdict for Agutyro in NTRK-Positive Solid Tumors

Bristol Myers Squibb is seeking a label expansion for its tyrosine kinase inhibitor Augtyro (repotrectinib), which the pharma wants to use in patients 12 years and above with locally advanced or metastatic solid tumors carrying the neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The FDA has set a target action date of June 15.

In its sNDA, which the FDA accepted and granted priority review in February 2024, BMS included data from the Phase I/II TRIDENT-1 study, which showed that Augtyro can elicit “clinically meaningful response rates” in patients. The response was durable, even in patients who had common resistance mutations.

The pharma also provided findings from the CARE study, which supplemented 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 works by blocking the proto-oncogene ROS1, as well as various tyrosine kinases. According to its label, his mechanism of action allows Augtyro to block fusion proteins containing ROS1 domains, which would otherwise trigger signaling cascades that culminate in the uncontrolled proliferation of cancer cells.

Augtyro was first approved in November 2023 for the treatment of advanced or metastatic non-small cell lung cancer patients positive for ROS1.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Correction (June 5): This story has been updated to remove Catalyst Pharmaceuticals’ sNDA for Firdapse. The FDA granted the application approval on May 30. BioSpace regrets the error.

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at tristan.manalac@biospace.com, tristan@tristanmanalac.com or on LinkedIn.