FDA Committee, in Reversal, Favors AMX0035 Approval for ALS

After rare 2nd review, advisors vote 7–2 to support Amylyx therapy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In a reversal, an advisory committee of the U.S. Food and Drug Administration (FDA) now says that the current evidence of efficacy of Amylyx Pharmaceuticals’ AMX0035 is sufficient to support its approval for amyotrophic lateral sclerosis (ALS).

The committee voted 7–2 in favor of AMX0035, Amylyx announced in a company press release.

The vote came at a rare second meeting to review additional analyses of trial data submitted by Amylyx in support of the therapy’s benefit in slowing disease progression and extending life.

“The Committee’s thoughtful review of the data and support of the benefit that AMX0035 may bring to the ALS community, if approved, is promising,” said Jamie Timmons, MD, Amylyx’s head of scientific communications.

Although the committee’s new vote is not binding, the FDA will consider it during its review of AMX0035. The agency is expected to announce its decision by September 29.

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In March, the same group of advisors — members of the Peripheral and Central Nervous System Drugs Advisory Committee, or PCNSDAC — narrowly voted against the combination therapy. At that time, the committee cited the small size of the CENTAUR Phase 2 clinical trial (NCT03127514), missing data, and questionable statistical analysis.

In an unusual development, the committee met again earlier this month to review all data on AMX0035 that is now available. Of the nine members, seven now voted that the evidence is sufficient to support AMX0035’s approval, while the other two voted against.

Questions on therapy’s efficacy

AMX0035 was conditionally approved in Canada earlier this year, and is now available in the country under the brand name Albrioza. It is also under reviewed by health authorities in Europe.

The therapy had received orphan drug designation in both the U.S. and Europe for the treatment of ALS. This status is meant to accelerate the therapy’s clinical development and regulatory review.

AMX0035 contains a fixed-dose combination of two compounds, called tauroursodeoxycholic acid and sodium phenylbutyrate, thought to protect nerve cells from damage. The experimental treatment is designed to be taken twice daily by mouth or via a feeding tube.

Amylyx’s application to the FDA seeking approval of AMX0035 was supported by data from the CENTAUR trial and its extension study.

CENTAUR compared the treatment against a placebo in 137 adults who had been recently diagnosed with rapidly progressing ALS. Top-line results showed the trial met its primary goal: after six months, AMX0035 significantly outperformed a placebo at slowing functional decline, as measured by the ALS Functional Rating Scale Revised.

After completing the six-month trial, 90 participants enrolled in its extension study, where all were treated with AMX0035.

Initial analyses of follow-up data spanning both CENTAUR and its extension study showed that the experimental therapy was associated with a 43% lower risk of death, prolonging patients’ life by a mean of 6.9 months relative to those initially assigned to a placebo.

Additional analyses — included in the second review by the FDA committee — suggested AMX0035 extended median survival time by more than 10 months, as compared with an estimated survival if patients had remained on a placebo for the full trial. This represented a 61% lower risk of death.

CENTAUR’s data “consistently demonstrated potential benefits of AMX0035 on function and overall survival, which is the first time this has been demonstrated in an ALS clinical trial,” Josh Cohen and Justin Klee, co-CEOs of Amylyx, said in statement emailed to ALS News Today.

“We believe the analyses all find the same thing—people with ALS on AMX0035 live substantially longer than people with ALS on standard of care,” they added.

The effectiveness and safety of AMX0035 in ALS patients are being further studied in a larger Phase 3 trial, called PHOENIX (NCT05021536). The study is recruiting adults with ALS who started experiencing symptoms within the past two year; enrollment is ongoing at dozens of sites across the U.S. and Europe.

“We are grateful to the advocacy community, our trial participants and their family members, the ALS clinicians, and countless others who continue to support our mission of ensuring that people living with ALS around the world can access promising new therapies as quickly and efficiently as possible,” Timmons said.

Notably, the Institute for Clinical and Economic Review (ICER), a U.S. nonprofit that assesses the cost-effectiveness of therapies, recently released its report on AMX0035. ICER concluded that the therapy is likely to offer clinical benefit on top of standard of care, and would be cost effective at an annual price of $9,100–$30,600.

“AMX0035 has the opportunity to be a meaningful new treatment option for physicians and the ALS community in the fight against ALS,” Cohen and Klee said in the statement.