Known as Relyvrio in the U.S., Amylyx’s AMX0035 may face a longer road to approval in Europe as the company reported that CHMP could reject its marketing authorization application.
Pictured, from left: Amylyx Co-CEOs Josh Cohen and Justin Klee/Courtesy Amylyx
United States: check. Canada: check. Europe: Not so fast for Amylyx’s amyotrophic lateral sclerosis drug, AMX0035. The company issued an update Tuesday stating that the European regulator is leaning toward a negative opinion on its marketing authorization application.
AMX0035, known as Relyvrio in the U.S. and Albrioza in Canada, is under an ongoing review with the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP).
Amylyx notched its first approval of AMX0035—a fixed-dose combination of two small molecules, sodium phenylbutyrate and taurursodiol—in June 2022 when Health Canada determined that data from the Phase II CENTAUR trial sufficiently demonstrated clinical benefit. The FDA followed in September, greenlighting Relyvrio as the country’s third drug for ALS, a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord.
ALS is uniformly fatal, typically claiming its victims between three to five years after diagnosis.
Should the CHMP indeed issue a negative opinion, Tammy Sarnelli, global head of regulatory affairs and clinical compliance at Amylyx, said the company would request a formal re-examination procedure. “We disagree with the current view expressed by the CHMP and remain confident in the data from the CENTAUR trial,” Sarnelli said in a prepared statement.
A formal re-evaluation would take approximately four months, according to the announcement. If required, the re-examination procedure would also be based on the current application and CENTAUR data, Amylyx Co-CEOs Josh Cohen and Justin Klee told BioSpace in an email.
A final decision on the marketing authorization application (MAA) is expected in late June when the CHMP holds its next meeting.
“There has not been a new product approved in the European Union for ALS in over 25 years,” said Stéphanie Hoffmann-Gendebien, head, general manager for international markets, EMEA at Amylyx, in the same press release. “While our MAA is under review, we remain committed to exploring all potential paths forward given people living with ALS have no time to wait.”
Phase III Data Expected in 2024
In the 24-week CENTAUR trial, 137 patients treated with Relyvrio experienced a slower rate of decline based on a clinical assessment of daily functioning compared to placebo, the FDA stated in its approval notice. Post-hoc analysis of the data showed a median survival benefit of 18.8 months, an improvement over the 6.9 months initially reported.
But the road to FDA approval was not a smooth one. In March 2022, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that the CENTAUR data was not sufficient to establish AMX0035’s efficacy in treating ALS. Then, in a rare second advisory committee, the external advisers voted 7-2 in favor of approving the drug, citing the post hoc analysis, the severity of ALS and the significant need for new treatments, BioSpace reported.
Health Canada approved AMX0035 with conditions that included the provision of data from the ongoing Phase III PHOENIX trial. Topline results from PHOENIX are expected in 2024.
Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter.
Correction, May 29: This story has been updated from its original version to clarify that an FDA advisory committee did not vote 6-4 against AMX0035’s approval in March 2022, but rather that data from the CENTAUR study was not sufficient to establish its efficacy in treating ALS. BioSpace regrets the error.
