One of the few amyotrophic lateral sclerosis drugs approved by the Food and Drug Administration failed a big clinical trial, and its manufacturer said Friday it was considering withdrawing it from the market.
The drug, called Relyvrio, was approved lower than two years ago, despite doubts about its effectiveness in treating severe neurological disorders. 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 of lack of functions similar to muscle control, speaking or respiration without assistance.
But the agency decided to provide the drug the green light reasonably than wait two years for results from a big clinical trial, citing data showing the treatment is secure and the desperation of patients suffering from a disease that always kills inside two to 5 years. Since then, about 4,000 patients in the United States have received the treatment, which is available in the type of a powder mixed with water and drunk or swallowed through a tube, which has a listing price of $158,000 a yr.
Now the results of a 48-week study involving 664 patients can be found, showing that the treatment works no higher than a placebo.
“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, co-CEOs of Amylyx Pharmaceuticals, the drug’s manufacturer, said in a press release. They said they might announce their plans for the drug inside eight weeks, “which may include a voluntary withdrawal” of it from the market.
“We will guide our decisions by two key principles: do what is right for people with ALS, based on information from regulators and the ALS community, and what the science tells us,” Mr. Klee and Mr. Cohen said.
There are only two other approved drugs for ALS in the United States: riluzole, approved in 1995, which may extend survival by several months, and edaravone, approved in 2017, which may slow the progression of the disease by about 33%.
Klee and Mr. Cohen conceived Relyvrio a couple of decade ago as undergraduate students at Brown University. Their idea was that a mix of taurursodiol, a complement sometimes used to control liver enzymes, and sodium phenylbutyrate, a drug utilized in children with urea disorders, could protect neurons in the brain against damage in diseases similar to ALS by stopping the dysfunction of two structures in cells: mitochondria and endoplasmic reticulum.
The FDA typically requires two compelling clinical trials, often Phase 3 trials, that are larger and more extensive than Phase 2 trials. For serious diseases requiring few treatments, the agency may accept one trial with additional supporting data. For Relyvrio, data got here from just one Phase 2 study during which 137 patients took the drug or placebo, and from an extension study during which some patients were followed after the end of the study while they were consciously taking the drug.
The agency initially really helpful that the company not seek approval of the drug until a Phase 3 trial is accomplished in 2024. ALS advocacy groups have waged a fierce campaign to influence the FDA to reconsider.
In March 2022, the FDA’s committee of independent advisors decided by a narrow majority that the treatment had not yet been shown to be effective, a conclusion also reached by the FDA Committee. 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 the report there agency reviewers said it also considered the latest data to be insufficient.
During that hearing, Dr. Billy Dunn, then director of the FDA’s Office of Neurology, asked the company whether, if the treatment was approved but then failed in a Phase 3 trial, it could voluntarily stop selling the drug.
Klee responded that if the study “is not successful, we will do what is right for patients, which includes voluntarily withdrawing the product from the market.”
That commitment, combined with emotional testimonies from patients and doctors, convinced seven members of the advisory committee to favor approval of the drug, with only two opposing it. Later that month, the FDA gave its approval, writing that there was “residual uncertainty about the evidence of effectiveness,” but “given the serious and life-threatening nature of ALS and the significant unmet need, this level of uncertainty is acceptable in this case.”
