One of the few treatments the Food and Drug Administration has approved for amyotrophic lateral sclerosis failed in a large clinical trial, and its manufacturer said Friday that it was considering removing it from the market.
The drug, called Relyvrio, was approved less than two years ago, despite doubts about its effectiveness in treating the serious 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 memory. unassisted breathing.
But the agency decided to give the drug the green light rather than wait two years for results from a large clinical trial, citing data showing the treatment is safe and the desperation of patients with a disease that often causes death in a period of 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 drunk or swallowed through a feeding tube and has a list price of $158,000 a year.
Now, results from the 48-week trial of 664 patients are available and showed that the treatment worked no better than a placebo.
“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, co-CEOs of Amylyx Pharmaceuticals, the treatment’s maker, said in a statement. They said they would announce their plans for the drug within eight weeks, “which could include voluntarily removing it” from the market.
“In our decisions we will be guided 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 tells us,” said Mr. Klee and the 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.
Klee and Cohen conceived Relyvrio about a decade ago when they were undergraduates at Brown University. Their idea was that the combination of taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for a pediatric urea disorder, could protect brain neurons from damage in diseases such as ALS by prevent the dysfunction of two structures in cells: the mitochondria. and the endoplasmic reticulum.
The FDA typically requires two persuasive clinical trials, typically 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 comes 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 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. ALS advocacy groups campaigned vehemently to persuade the FDA to reconsider its decision.
In March 2022, an independent advisory committee to the FDA narrowly decided that the treatment had not yet been proven effective, a conclusion also reached by the FDA. The 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 filed there, agency reviewers They said they also considered the new data insufficient.
At that hearing, Dr. Billy Dunn, then director of the FDA’s office of neuroscience, asked the company whether, if the treatment received approval but then failed in the Phase 3 trial, it would voluntarily stop selling the drug.
Klee responded that if the trial “is not successful, we will do what is right for patients, including voluntarily withdrawing the product from the market.”
That commitment, plus emotional testimony from patients and doctors, persuaded seven members of the advisory committee to favor approval, with only two opposed. Later that month, the FDA granted approval, writing that there was “residual uncertainty about the evidence of efficacy,” but that “given the serious and life-threatening nature of ALS and the significant unmet need, this level of uncertainty is acceptable.” In this instance”.
