One of the few Food and Drug Administration-approved treatments for amyotrophic lateral sclerosis failed a large clinical trial, and its maker said Friday it is considering pulling it from the market.
The drug, called Relyvrio, was approved less than two years ago despite questions about its effectiveness in treating the severe neurological disorder. At the time, FDA reviewers had concluded that there was not yet enough evidence that the drug could help patients live longer or slow the rate at which they lose functions such as muscle control, speech or unassisted breathing.
But the agency decided to give the drug the go-ahead rather than wait two years for the results of a large clinical trial, citing data showing the treatment is safe and the desperation of patients with a disease that often kills 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 swallowed through a feeding tube and has a list price of $158,000 a year.
Now, the results of the 48-week trial with 664 patients are available and showed that the treatment worked no better than a placebo.
“We are surprised and deeply disappointed,” said Justin Klee and Joshua Cohen, co-CEOs of Amylyx Pharmaceuticals, the treatment’s maker. They said they would announce their plans for the drug within eight weeks, “which may include its voluntary withdrawal” from the market.
“We will be guided in our decisions by two key principles: doing what is right for people living with ALS, informed by regulators and the ALS community, and by what the science tells us,” Mr. Klee and Mr. Cohen said.
There are only two other drugs approved for ALS 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 undergraduates at Brown University. Their idea was that the combination of taurosodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a drug for a pediatric uric acid disorder, could protect neurons in the brain from damage in diseases such as ALS, by preventing two structures in cells from malfunctioning: mitochondria. and the endoplasmic reticulum.
The FDA usually requires two conclusive clinical trials, usually Phase 3 trials, which are larger and more extensive than Phase 2 studies. For serious diseases with few treatments, the agency may accept one trial plus additional confirmatory data. For Relyvrio, the data came only from a Phase 2 trial in which 137 patients received either the drug or a placebo, as well as an extension study that followed some patients after the trial ended while 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 is completed in 2024. ALS advocacy groups campaigned hard to get the FDA to reconsider.
In March 2022, a panel of independent FDA advisors decided by a narrow margin that the treatment had not yet been proven effective, a conclusion also reached by the The FDA reviewers themselves. The agency then allowed Amylyx to submit more data and took the unusual step of scheduling a second independent advisory panel in September 2022. In a report presented there, agency reviewers they said they also find the new data insufficient.
At that hearing, Dr. Billy Dunn, then director of the FDA’s office of neuroscience, asked the company if, if the treatment was approved but later failed a Phase 3 trial, it would voluntarily stop selling the drug.
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.”
This commitment, as well as emotional testimony from patients and doctors, convinced seven members of the advisory committee to favor approval, with only two opposed. Later that month, the FDA granted approval, writing that there was “remaining uncertainty about the efficacy evidence” but that “given the severe and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this case.”