Amylyx Notches First Regulatory Win for ALS Drug in Canada

Amylyx CEOs Josh and Justin_Amylyx Pharmaceuticals

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

Shares of Amylyx Pharmaceuticals are up more than 3% in premarket trading following the announcement that its amyotrophic lateral sclerosis (ALS) therapy, AMX0035, has been approved for use in Canada. The approval, the company’s first, comes about ten days after the Amylyx was notified about a delay for potential approval in the United States.

The approval of AMX0035, marketed under the brand name Albrioza, marks the first new ALS drug approved in Canada since 2018. Albrioza is a fixed-dose combination of two small molecules, sodium phenylbutyrate and taurursodiol. It is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases. It was approved as a stand-alone treatment based on data from the Phase II CENTAUR trial.

posthoc analysis of data from the CENTAUR study announced in May showed a 10.6-month longer median survival duration for AMX0035 participants. That analysis used a rank-preserving structural failure time model, which is often used in oncology studies to account for placebo crossover. Data from that subgroup analysis showed that patients who received Albrioza saw an 18.8-month longer median survival duration than participants who did not receive the medication. 

The company said at the time that the analysis suggested a larger survival benefit for ALS patients who received the medication when making that placebo crossover adjustment. The original CENTAUR data suggested a median survival duration of 6.9 months. Detailed data from the CENTAUR study was published in multiple publications, including the New England Journal of Medicine and the Journal of Neurology, Neurosurgery and Psychiatry

In a joint statement, Justin Klee and Joshua Cohen, the co-founders and co-chief executive officers of Amylyx, touted the approval of Albrioza. The two said they have been committed to developing a new therapy for ALS for nearly a decade.

“We are excited with Health Canada’s decision to approve ALBRIOZA with conditions. Albrioza is a therapy that demonstrated in our CENTAUR trial a statistically significant and clinically meaningful impact on function, alone or in addition to existing ALS therapies. We are grateful to the people who participated in our clinical trials, their families, the researchers and the ALS community for helping to make this milestone happen,” Klee and Cohen said.

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 with ALS lose the ability to control muscle movement, which eventually leads to total paralysis and 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. In Canada, it is estimated that approximately 3,000 Canadians are living with ALS. The average life expectancy from symptom onset is two to five years.

Earlier this month, the U.S. Food and Drug Administration delayed its timeline for potentially approving AMX0035. The extension was added to allow regulators time to review the post hoc data announced in May. The FDA considered that data a major amendment to its New Drug Application. 

The post hoc analysis was presented about two months after the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted six to four against recommending approval of the experimental drug. The committee members were largely opposed to the CENTAUR trial design. There were also questions regarding the initial survival benefit. 

It is possible the FDA will greenlight AMX0035 under conditions related to clinical outcomes from the ongoing Phase III PHOENIX study, as Health Canada already has. The primary endpoint of the PHOENIX trial will include safety and efficacy, as well as the potential impact of AMX0035 on disease progression over 38 weeks. Amylyx anticipates topline results from the PHOENIX trial in 2024.

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