Agencies hope for more data before deciding on approval.
It's not uncommon for a neuroscience treatment—like Amylyx's AMX0035 for the treatment of ALS-- to look good in small, early trials and then not stand up in larger, phase 3 trials. That is why the FDA required further review in March before it would approve AMX0035.
That review will happen on Sept. 7, when the FDA Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) will reconvene to discuss the New Drug Application (NDA) for AMX0035, also called Albrioza. The PCNSDAC met on March 30 to discuss the NDA but voted 6-4 to deny approval based on the fact that the available data on the drug's effectiveness didn't meet the criteria for approval. The FDA will announce the scheduling of the PCNSDAC meeting in the Federal Register.
The company's initial submission to the FDA was based on results from its CENTAUR trial, a multicenter Phase 2 clinical trial with 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. Amylyx has already started a larger trial with about 600 patients globally, which is expected to be completed in 2024. According to the company, the initial trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised.
"Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group," a press release stated.
Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle and Nerve.
The FDA reports that discussions on September 7 will focus on the additional analyses of data from the company’s clinical studies that the FDA determined to be a major amendment to the NDA.
PCNSDAC members questioned the Amylyx study due to "the small size of the trial, the possibility that patients could tell whether they were receiving the drug or placebo, the high percentage of participants in the drug portion who dropped out and the company’s definition of “death,” which included hospitalizations and tracheotomies in addition to actual deaths," reported Bloomberg in an opinion piece back in March.
The treatment has already been approved in Canada in June, with certain conditions, including release of data from the ongoing global late-stage study. The oral fixed-dose medication is also awaiting approval by the European Medicines Agency. The FDA is expected to make its decision on September 29.
According to the Christopher and Dana Reeves foundation, some of the $200 million raised by the Ice Bucket ALS challenge over the past six years has gone toward research involving AMX0035. The foundation described the drug as "one of the most significant findings in development" for ALS. The CENTAUR trial was also funded, in part, by the ALS ACT grant and supported by The ALS Association, ALS Finding a Cure, the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General.
The news of the Sept. 7 meeting shot up shares of the company about 13% to $21.91 earlier this week.
Robin Robinson is a contributing writer for HealthLeaders.
KEY TAKEAWAYS
The FDA's Peripheral and Central Nervous System Drugs Advisory Committee will reconvene on Sept. 7 to discuss the New Drug Application for AMX0035, also called Albrioza.
The PCNSDAC met on March 30 to discuss the NDA but voted 6-4 to deny approval based on the fact that the available data on the drug's effectiveness didn't meet the criteria for approval.
The company's initial submission to the FDA was based on results from its multicenter Phase 2 clinical trial with 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase.