Amylyx ALS drug’s winding regulatory path leads to long-awaited FDA approval

Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.

Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.


The FDA has approved an Amylyx Pharmaceuticals drug for amyotrophic lateral sclerosis (ALS), bringing patients a much needed additional therapy for this rare and fatal neuromuscular disorder that has few treatments.

The regulatory decision announced late Thursday makes the drug, formerly known as AMX0035, just the third FDA-approved treatment for ALS. Cambridge, Massachusetts-based Amylyx will market the drug—its first product—under the name “Relyvrio.”

The cause of ALS is not known but it is characterized by the death of motor neurons that lead to a progressively worsening loss of muscle control. FDA approval of Relyvrio was based on a placebo-controlled Phase 2 clinical trial that enrolled 137 adults. Results showed that those treated with the Amylyx drug experienced a slower rate of decline, measured using a clinical assessment for ALS patients. Additional analysis of the data after the study was done found patients who received the test drug survived longer than those given a placebo. No serious adverse events were reported from the study. The most common side effects included diarrhea, abdominal pain, nausea, and upper respiratory tract infection.

Last year, the FDA said Amylyx would need data from a larger Phase 3 study to support a regulatory submission. The agency reconsidered its position after discussions with the company. Last November, Amylyx submitted a new drug application based on the Phase 2 data while it also proceeded with plans for a Phase 3 clinical trial.

In March, an independent advisory committee to the FDA voted against recommending approval of the Amylyx drug. Committee members were not persuaded by the analysis of the study results. But the company won a reprieve with the unusual reconvening of the advisory committee. At that second meeting, held earlier this month, Amylyx executives committed to withdraw their drug from the market if a confirmatory study did not show patient benefit. The committee then agreed, by a 7 to 2 vote, that the available evidence is enough to support approval of AMX0035 for the treatment of ALS. In approving the Relyvrio based on a single study, the FDA says it is being flexible, according to the agency’s summary documents about the drug’s review.

“Exercising regulatory flexibility, the single study with positive results on a clinically meaningful primary outcome accompanied by confirmatory evidence of an observed survival benefit provides substantial evidence of effectiveness,” the FDA said. “The benefits of AMX0035 outweigh the risk, as the drug appears well tolerated without any significant safety signals of concern.”

The Amylyx drug is a combination of two compounds, tauroursodeoxycholic acid and sodium phenylbutyrate, which together are intended to lead to longer survival of neurons. The two main components of the drug are not proprietary to Amylyx. Tauroursodeoxycholic acid, or Turso, is commercially available as a nutritional supplement. Relyvrio is a proprietary fixed-dose combination of the molecules. It comes as a powder that is mixed in water and taken by mouth.

Relyvrio is the first FDA-approved ALS drug since 2017, when the agency green lit Mitsubishi Tanabe Pharma’s Radicava. The intravenously infused drug is meant to slow the nerve damage associated with ALS symptoms. The affirmative regulatory decision was based on clinical data showing functional benefit according to a scale that assesses the disease’s symptoms. The FDA approved an oral version of Radicava in May, providing patients a formulation that they can take at home.

The first FDA-approved ALS therapy was riluzole, a now generic tablet that passed regulatory muster in 1995. Though that drug improved early survival in patients, the FDA notes that it did not show benefit on measures of muscle and neurological function.

Amylyx has not yet disclosed the price for Relyvrio. In a statement, Chief Commercial Officer Margaret Olinger said she expects the drug will become available in the next four to six weeks.

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