ALS drug Relyvrio fails clinical trial, could be pulled from market

ALS drug Relyvrio fails clinical trial, could be pulled from market

One of the few treatments approved by the Food and Drug Administration for amyotrophic lateral sclerosis failed in a large clinical trial, and its manufacturer said Friday it plans to pull 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 disorder. At the time, FDA reviewers concluded that there was not yet sufficient evidence that the drug could help patients live longer or slow the rate at which they lose functions such as control muscle, speech or breathing without assistance.

But the agency decided to greenlight the drug instead of waiting two years for results from a large clinical trial, citing data showing the treatment is safe and the desperation of patients with the disease. which often results in death within two to five years. Since then, about 4,000 patients in the United States have received the treatment, a powder mixed with water and drunk or ingested through a feeding tube, at a list price of $158,000 a year.

Today, results from the 48-week trial involving 664 patients are available and show that the treatment worked no better than a placebo.

“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, co-chief executive officers 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 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 tells us,” they said. said Mr. Klee and Mr. said Cohen.

There are only two other ALS drugs approved 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%.

Mr. Klee and Mr. Cohen designed Relyvrio about a decade ago while they were undergraduates at Brown University. Their idea was that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for pediatric urea disorder, could protect neurons in the brain from damage caused by diseases like ALS by preventing the dysfunction of two structures in cells: the mitochondria. and the endoplasmic reticulum.

The FDA generally requires two compelling clinical trials, typically Phase 3 trials, which are larger and more in-depth than Phase 2 studies. For serious illnesses requiring few treatments, the agency may accept one trial plus data additional confirmations. For Relyvrio, the data comes only from a phase 2 trial in which 137 patients took either the drug or a placebo, as well as an extension study that followed some patients after the trial ended then that they knowingly took the medication.

The agency initially recommended that the company not seek approval of the drug until after the Phase 3 trial was completed in 2024. ALS advocacy groups campaigned vehemently to persuade the FDA to reconsider its decision.

In March 2022, a committee of independent FDA advisors decided by a narrow majority that the treatment had not yet demonstrated effectiveness, a conclusion also reached by the FDA. FDA’s own reviewers. The agency then authorized Amylyx to submit more data and took the unusual step of scheduling a second meeting of the independent advisory committee in September 2022. In a report presented there, agency evaluators 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 was approved but later failed the Phase 3 trial, it would voluntarily stop selling medication.

Mr. Klee responded that if the trial “fails, we will do what is right for patients, which includes voluntarily removing the product from the market.”

This commitment, along with moving testimonials from patients and doctors, persuaded seven members of the advisory committee to speak in favor of approval, compared to only two who opposed it. 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 need not satisfied, this level of uncertainty is acceptable in this instance.

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David B.Otero

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