EMA branch opposes conditional approval of AMX0035 in Europe

CHMP questions ALS therapy's effectiveness, Amylyx likely to appeal

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by Steve Bryson, PhD |

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The Committee for Medicinal Products for Human Use (CHMP) has issued an opinion opposing Amylyx Pharmaceuticals’ bid for conditional European Union approval of AMX0035, its oral treatment to slow the progression of amyotrophic lateral sclerosis (ALS).

The negative recommendation from the advisory committee, an arm of the European Medicines Agency (EMA), is not binding. But the EMA will consider the opinion when making its final approval decision, while Amylyx intends to request that CHMP reconsider its findings.

According to the EMA, the committee had concerns that data from the CENTAUR trial (NCT03127514), on which the application was based, did not “convincingly show” that AMX0035 was effective at slowing ALS progression.

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Survival findings also were “unreliable,” the opinion stated, given how these data were collected and analyzed. In support of its decision, advice from expert groups, including neurology specialists and patient representatives, was considered.

The therapy is approved in the U.S. under the name Relyvrio (sodium phenylbutyrate and taurursodiol) and in Canada as Albrioza — the brand name that will be used in Europe should it be approved.

“We are confident in the strength of our CENTAUR trial data, which we believe meets the criteria for conditional approval. These data were also the basis of the full approval received from the U.S. Food and Drug Administration and the approval with conditions from Health Canada,” Tammy Sarnelli, global head of regulatory affairs and clinical compliance at Amylyx, said in a company press release. “We disagree with the CHMP’s opinion and will request a formal re-examination procedure of the current Marketing Authorisation Application (MAA).”

Filing for a formal reconsideration of the application starts a process that takes about four months. Based on an evaluation by a different set of examiners than those of the initial assessment, the process will close with CHMP adopting a final opinion.

“We will continue to engage with CHMP and EMA through the re-examination process with the goal of making Albrioza available in Europe as it is in the United States and Canada,” said Joshua Cohen and Justin Klee, Amylyx’s co-CEOs. “We know how precious time is for people with ALS and their families.”

Although it is not clear how AMX0035 works, its two active ingredients, sodium phenylbutyrate and ursodoxicoltaurine (taurursodiol in the U.S), are thought to reduce the nerve cell damage that causes ALS and slow the progression of disease symptoms.

Findings of Phase 3 trial of AMX0035 in ALS patients likely in mid-2024

Data from CENTAUR, a Phase 2 trial that enrolled 137 adults with rapidly progressing ALS, supported its conditional approval in Canada and its U.S approval.

Meeting its primary goal, the trial showed that AMX0035 significantly slowed disability progression compared with a placebo. Data spanning CENTAUR and its open-label extension study also supported a 10-month survival benefit in people assigned to AMX0035 from the start.

A Phase 3 trial called PHOENIX (NCT05021536) is underway to confirm AMX0035’s safety and efficacy in 664 ALS patients at sites across the U.S. and Europe. The new trial is fully enrolled, with top-line data expected by June 2o24.

“While our MAA continues to be under review, we will also work towards completing our global Phase 3 PHOENIX study, with topline results anticipated in mid-2024, which will provide important additional data on the efficacy and safety profile of Albrioza,” said Stéphanie Hoffmann-Gendebien, general manager at Amylyx. “There have been no new innovations approved in Europe for this devastating disease in over 25 years, and we recognize the urgent need of the ALS community in Europe to access new treatment options.”

CHMP’s negative opinion will not affect patients currently enrolled in clinical trials of AMX0035, Amylyx stated. It encourages study participants needing further information to speak with their clinical trial physician.