A novel combination of sodium phenylbutyrate and taurursodiol (Relyvrio) was approved to treat patients with amyotrophic lateral sclerosis (ALS), the on Thursday.
"This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure," said Billy Dunn, MD, the director of the Office of Neuroscience at FDA's Center for Drug Evaluation and Research.
The drug, also known as AMX0035, slowed functional decline in the phase II CENTAUR trial of ALS patients, most of whom were already taking two FDA-approved ALS medications, riluzole (Rilutek) and edaravone (Radicava).
On September 7, FDA advisors voted 7-2 to support approval of sodium phenylbutyrate-taurursodiol for ALS. On March 30, however, that same advisory panel voted 6-4 that data from the CENTAUR study did not support a conclusion that the combination was effective and that more evidence was needed.
Drug developer Amylyx Pharmaceuticals came to the September advisory committee meeting with additional survival data from CENTAUR and its open-label extension, which FDA staff reviewers said did not provide independent confirmatory evidence of the clinical effect of sodium phenylbutyrate and taurursodiol in ALS.
But at that September meeting, Dunn emphasized that ALS drugs may require more flexibility than usual from regulators, which helped sway some advisors to rethink their earlier position.
"I voted yes. I voted no last time," Thomas Montine, MD, PhD, of Stanford University in California, said at the time. "The seriousness of the disease, the unmet medical need, the moving testimonies of patients and families, the consistent testimony of experts in treating patients with ALS ... although there are still limitations, in aggregate, my judgement was for yes, to support."
In the clinical trial, the most common adverse reactions experienced were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Taurursodiol is a bile acid and may cause worsening diarrhea in patients with disorders that interfere with bile acid circulation, the FDA warned.
Sodium phenylbutyrate-taurursodiol can be taken orally by combining a packet in water or can be given by feeding tube. The recommended dosage for the first 3 weeks is one packet (3 g sodium phenylbutyrate and 1 g taurursodiol) daily. After 3 weeks, the dosage increases to two packets a day. The medication can be taken as a monotherapy or with existing approved treatments, .
The phase III trial of sodium phenylbutyrate-taurursodiol is scheduled to have topline results in 2024. If that study reads out negative, Amylyx co-CEO Justin Klee told FDA advisors his company will "do what is right for patients," which includes voluntarily removing the drug from the market.
The ALS community has strongly urged the FDA to be more flexible about new drugs, given the devastating effect of the disease. Lawmakers also have pressed the FDA to get new ALS therapies to patients.
In June, Canada became the to approve sodium phenylbutyrate-taurursodiol (marketed there as Albrioza) for ALS, contingent on the provision of data from the PHOENIX trial.