One of the few treatments approved by the Food and Drug Administration for amyotrophic lateral sclerosis has failed a major clinical trial, and its manufacturer said Friday it is considering whether to pull it off the market.
The drug, called Relyvrio, was approved less than two years ago, despite questions about its effectiveness in treating severe neurological disorders. At the time, FDA reviewers concluded that there was not enough evidence that the drug could help patients live longer or slow the rate of loss of functions such as muscle control, speech or breathing without help
But the agency decided to greenlight the drug 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 the disease that often causing 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 swallowed through a feeding tube and has a list price of $158,000 a year.
Now, the results of the 48-week trial of 664 patients are in, and they show that the treatment did not work better than a placebo.
“We are surprised and very 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 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 regulatory authorities and the ALS community, and by what the science,” Mr. Klee and Mr. said Cohen.
There are only two other approved ALS drugs 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 .
Conceived by Mr. Klee and Mr. Cohen and Relyvrio about a decade ago as undergraduate students at Brown University. Their idea is that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a drug for a pediatric urea disorder, might protect neurons in the brain from damage in diseases such as ALS by preventing the dysfunction of two structures in cells: mitochondria and the endoplasmic reticulum.
The FDA typically requires two persuasive clinical trials, usually Phase 3 trials, which are larger and more comprehensive than Phase 2 studies. For chronic diseases with minimal treatment, the agency may accept a test and additional confirmatory data. For Relyvrio, the data came only from a Phase 2 trial in which 137 patients took the drug or a placebo, plus an extension study that followed some patients after the trial when they were deliberately taking medicine.
The agency initially recommended that the company not apply for the drug’s approval until Phase 3 trials were completed in 2024. ALS advocacy groups campaigned hard to persuade the FDA to reconsider consider.
In March 2022, a committee of independent advisors to the FDA decided by a narrow margin that the treatment had not yet been proven effective, a conclusion also reached by FDA’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 examiners they said the new data wasn’t enough either.
In that hearing, Dr. Billy Dunn, then the director of the FDA’s office of neuroscience, asked the company whether, if the treatment received approval but later failed in Phase 3 testing, it would voluntarily stop selling the drug.
Mr. answered Klee said that if the trial is “unsuccessful, we will do the right thing for patients, which includes voluntarily removing the product from the market.”
That promise, along with emotional testimony from patients and doctors, persuaded the seven members of the advisory committee to favor approval, with only two dissenting. Later that month, the FDA granted approval, writing that there was “remaining uncertainty about the evidence of effectiveness,” but that “given the serious and life-threatening nature of ALS and the substantial unmet need, the level of uncertainty is acceptable in this instance.”
