One of the few treatments the Food and Drug Administration has approved for amyotrophic lateral sclerosis has failed a large clinical trial, and its manufacturer said Friday that it was considering whether to withdraw it from the market.
The medication, called Relyvrio, was approved less than two years ago, despite questions about its effectiveness in treating the severe neurological disorder. At the time, the F.D.A.’s reviewers had concluded there was not yet sufficient evidence that the medication could help patients live longer or slow the rate at which they lose functions like muscle control, speaking or breathing without assistance.
But the agency decided to greenlight the medication instead of waiting two years for results of a large clinical trial, citing data showing the treatment to be safe and the desperation of patients with a disease that often causes death within two to five years. Since then, about 4,000 patients in the United States have received the treatment, a powder that is mixed with water and either drunk or ingested through a feeding tube and carries a list price of $158,000 a year.
Now, results of the 48-week trial of 664 patients are in, and they showed that the treatment did not work better than a placebo.
“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, the co-chief executive officers of Amylyx Pharmaceuticals, the treatment’s manufacturer, said in a statement. They said they would announce their plans for the medication within eight weeks, “which may include voluntarily withdrawing” it from the market.
“We will be led in our decisions by two key principles: doing what is right for people living with A.LS., informed by regulatory authorities and the A.L.S. community, and by what the science tells us,” Mr. Klee and Mr. Cohen said.
There are only two other approved A.L.S. medications in the United States: riluzole, approved in 1995, which can extend survival by several months, and edaravone, approved in 2017, which can slow progression by about 33 percent.
Mr. Klee and Mr. Cohen conceived of Relyvrio about a decade ago as undergraduate students at Brown University. Their idea was that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for a pediatric urea disorder, could protect neurons in the brain from damage in diseases like A.L.S. by preventing dysfunction of two structures in cells: mitochondria and the endoplasmic reticulum.
The F.D.A. typically requires two persuasive clinical trials, usually Phase 3 trials, which are larger and more extensive than Phase 2 studies. For serious diseases with few treatments, the agency can accept one trial plus additional confirmatory data. For Relyvrio, the data came only from one Phase 2 trial in which 137 patients took either the drug or a placebo, plus an extension study that followed some patients after the trial ended when they were knowingly taking the drug.
The agency initially recommended that the company not apply for approval of the drug until the Phase 3 trial was completed in 2024. A.L.S. advocacy groups campaigned vehemently to persuade the F.D.A. to reconsider.
In March 2022, a committee of independent advisers to the F.D.A. decided by a narrow margin that the treatment had not yet been shown to be effective, a conclusion also reached by the F.D.A.’s own reviewers. The agency then allowed Amylyx to submit more data and took the unusual step of scheduling a second independent advisory committee meeting in September 2022. In a report presented there, agency reviewers said they also considered the new data insufficient.
At that hearing, Dr. Billy Dunn, then the director of the F.D.A.’s office of neuroscience, asked the company whether, if the treatment received approval but later failed the Phase 3 trial, it would voluntarily stop selling the medication.
Mr. Klee responded that if the trial “is not successful, we will do what is right for patients, which includes voluntarily removing the product from the market.”
That commitment, plus emotional testimony from patients and doctors, persuaded seven advisory committee members to favor approval, with only two opposing. Later that month, the F.D.A. granted the approval, writing that there was “residual uncertainty about the evidence of effectiveness,” but that “given the serious and life-threatening nature of A.L.S. and the substantial unmet need, this level of uncertainty is acceptable in this instance.”
