FDA Approves Third-Ever Drug for ALS - Amylyx's AMX0035 (Updated)

From left: Amylyx Co-CEOs Josh Cohen and Justin Klee/Courtesy Amylyx

The biopharma world - and markets - spent Thursday evening reacting after the FDA gave the green light to only its third-ever drug for ALS, Amylyx's AMX0035. 

Shares of Amylyx rose 14 percent in extended trading Thursday before falling 7 percent after the company confirmed an initial annual price of $158 thousand for Relyvrio ($12.5 thousand for a 28-day supply) Friday morning. 

The new ALS drug, a combination of sodium phenylbutyrate and taurursodiol, was approved after clinical data showed the medication slowed the progression of the disease, extending the lives of patients by several months. AMX0035 will be sold under the brand name Relyvrio.

The approval comes weeks after the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee met for the second time and ultimately endorsed AMX0035 in a 7-2 vote. The green light was based on a post hoc analysis of data that showed a 10.6-month longer median survival duration for patients who received the drug. The updated median survival of 18.8 months was an improvement over the 6.9 months initially reported.

This data came from the Phase II CENTAUR trial, which used a rank-preserving structural failure time model to assess median survival data. Patients treated with AMX0035 experienced a slower rate of decline based on a clinical assessment of daily functioning compared to those receiving a placebo. 

Data from a larger Phase III study dubbed PHOENIX is expected to be read out in 2024. The company anticipates this study will provide confirmation that AMX0035 is beneficial to patients.

The primary endpoints of the PHOENIX trial will include safety and efficacy, as well as the potential impact of AMX0035 on disease progression over 38 weeks. The Phase III trial caused advisory committee members to be more at ease prior to the vote earlier this month.

Josh Cohen and Justin Klee, co-chief executive officers at Amylyx, expressed their excitement about the FDA approval, the company's second after AMX0035 was first authorized in Canada. The drug is marketed as Albrioza in that country. 

This was not only an important regulatory win for the company, Cohen and Klee stated, but also for the ALS community.

Klee and Cohen said the company’s goal is that every ALS patient who is eligible for the new ALS drug will have access to the medication as quickly as possible.

“We know people with ALS and their families have no time to wait. Our teams are in place and ready to help people living with ALS gain access to this important new therapeutic option,” the co-CEOs said in a statement e-mailed to BioSpace.

Cohen and Klee thanked the ALS community for supporting the company throughout its research endeavors and helping to bring Relvrio through to commercialization.

“We promise to continue to make our decisions in partnership with stakeholders in the community. We owe it to all of them and every family to do this right, starting with access and continuing to invest in commercialization efforts, research and pipeline expansion, as we always have, to further our mission of ending the suffering caused by neurodegenerative diseases,” they wrote.

Dr. Merit Cudkowicz, a Harvard professor, chair of neurology, director of The Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital and co-principal investigator of the CENTAUR trial said it was a great day for people living with ALS, as well as those researchers who strive to bring new treatments to them.

“I am beyond happy. Now our patients have another option. ALS has huge unmet need and the FDA has shown flexibility and understanding of the illness and need,” Cudkowicz told BioSpace.

Stacy Lindborg, Ph.D., EVP and chief development officer at BrainStorm Cell Therapeutics congratulated Amylyx on the milestone. 

"At BrainStorm, we commend the people of Amylyx for their perseverance and we celebrate with the ALS community, who now will have access to another treatment option to combat this unrelenting disease," she said in an e-mailed statement. 

BrainStorm announced its intentions in August to submit a Biologics License Application for its own ALS candidate, NurOwn. 

Nicole Cimbura, co-lead of the I AM ALS Legislative Affairs Team at I AM ALS expressed hope for the future. 

"FDA approval of AMX0035 with one randomized controlled trial demonstrates that the FDA exercised regulatory flexibility as promised in the 2019 ALS Guidance document," said Cimbura, who lost her husband to ALS.  

The guidance document for ALS clinical trials, issued in September 2019, was a precursor to the more recent FDA Action Plan for Rare Neurodegenerative Diseases, Including ALS. 

Also known as Lou Gehrig’s disease, ALS is a progressive neurodegenerative disease that negatively affects neurons in the brain and the spinal cord. Patients lose the ability to control muscle movement, which eventually leads to total paralysis and, ultimately, death. It is estimated that approximately 12,000 to 15,000 Americans have ALS, with about 5,000 to 6,000 new cases diagnosed annually. 

Klee and Cohen added that healthcare providers are authorized to begin writing prescriptions for Relyvrio through a comprehensive support program the company is implementing. Details of the program will be forthcoming, according to the announcement.