ALS drug Relyvrio fails in clinical trial and may be withdrawn from the market

One of the few treatments the Food and Drug Administration has approved for amyotrophic lateral sclerosis has failed a major clinical trial, and the manufacturer said Friday it was considering whether to withdraw it from the market.

The drug, called Relyvrio, was approved less than two years ago despite questions about its effectiveness in treating the serious neurological condition. At the time, FDA reviewers 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 breathing without assistance.

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 occurs within two to will result in death for 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 taken through a feeding tube and has a suggested retail price of $158,000 per year.

Now the results of the 48-week trial involving 664 patients are in and showed that the treatment worked no better than a placebo.

“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, the co-CEOs 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 voluntarily withdrawing it from the market.”

“We will be guided by two key principles in our decisions: doing what is right for people with ALS, informed by regulators and the ALS community, and by what science tells us,” said 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.

Mr. Klee and Mr. Cohen conceived of Relyvrio about a decade ago as students at Brown University. Their idea was that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a drug for urea disorder in children, could protect neurons in the brain from damage in diseases such as ALS, through dysfunction of two structures occur in cells: mitochondria. and the endoplasmic reticulum.

The FDA typically requires two compelling clinical trials, usually Phase 3 trials, which are larger and more comprehensive than Phase 2 trials. For serious diseases with few treatments, the agency may accept one study plus additional confirmatory data. For Relyvrio, the data only came from one Phase 2 study in which 137 patients took the drug or a placebo, plus an extension study that followed some patients after the study ended when they were consciously taking the drug.

The agency initially recommended that the company not seek approval for the drug until the Phase 3 trial was completed in 2024. ALS advocacy groups campaigned vigorously to convince the FDA to reconsider.

In March 2022, a committee of independent advisors to the FDA decided by a narrow margin that the treatment had not yet proven effective, a conclusion also reached by the FDA. FDA’s own reviewers. The agency then allowed Amylyx to submit more data and took the unusual step of scheduling a second meeting of the independent advisory committee for September 2022. In a report presented there: agency reviewers said they also considered the new data to be insufficient.

During that hearing, Dr. Billy Dunn, then director of the FDA’s Office of Neurosciences, asked the company whether, if the treatment were approved but later failed the 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, including voluntarily withdrawing the product from the market.”

That commitment, plus emotional testimonials from patients and doctors, convinced seven members of the advisory committee to give approval, while only two opposed. Later that month, the FDA granted approval, writing that there was “residual uncertainty regarding the evidence of effectiveness,” but that “given the serious and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this sample. ”