FDA Extends Review for Amylyx ALS Drug to September

Amylyx Co-CEOs Justin Klee and Joshua Cohen/Courtesy of Amylyx Pharmaceuticals.

Massachusetts-based Amylyx Pharmaceuticals shared news Friday that the U.S. Food and Drug Administration (FDA) has extended the review period for AMX0035, a combination drug treatment with the potential to treat patients with amyotrophic lateral sclerosis (ALS). The new Prescription Drug User Fee Act (PDUFA) review date is scheduled for September 29.

PDUFA dates can be pushed if additional information is given to the FDA that affects the review, such as a change in clinical data or manufacturing. In this case, Amylyx submitted additional analyses of data from its clinical studies, warranting the FDA’s request for more time.

AMX0035 is a combination therapy comprised of sodium phenylbutyrate and taurursodiol. The components respectively are a chaperone molecule and a Bax inhibitor. Together, the mechanism aims to block particular cell pathways that occur within the patient’s endoplasmic reticulum and mitochondria. These pathways play a role in cellular death that is seen in ALS neurodegeneration. By successfully interrupting these pathways, the unfolded protein response and cellular death process would be halted.

In March, ahead of the previously scheduled PDUFA date, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted on whether approval of AMX0035 is adequately supported through safety and efficacy data. This committee voted 6 to 4 against approval. Committee members questioned the moderate 6.9-month survival benefit as well as a lack of clinically significant benefit observed between the placebo and experimental group.

In response to the committee’s decision, the post hoc analysis was conducted to utilize the rank-preserving structural failure time model. This model allows for the data to account for the placebo crossover that occurred in the Phase II trial. This means that all participants began in either the experimental or placebo group and were later reassigned to the opposite group as part of the study design. The new analysis demonstrates a substantial increase in the participants’ median survival duration, from 6.9 months up to 10.6-18.8 months.

Justin Klee and Joshua Cohen, co-CEOs and co-founders of Amylyx commented on Friday’s news:

“We are confident in the potential of AMX0035 to help people living with ALS and other neurodegenerative diseases, and we continue to work closely with the FDA as they complete their review.”

A Phase III  48-week, randomized placebo-controlled global clinical trial, entitled Phoenix, is currently underway to further evaluate the safety and efficacy of AMX0035 in ALS. The primary endpoint from an efficacy standpoint will be a composite measure of survival and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks along with survival and tolerability over the 48 weeks. 

In the future, Amylyx hopes to explore AMX0035 treatment indicated for other neurodegenerative diseases, which could include Parkinson’s, Alzheimer’s or other diseases with a high degree of unmet medical need.