Special for Infobae of The New York Times.
The US Food and Drug Administration (FDA) on Thursday approved an experimental treatment for amyotrophic lateral sclerosis, or ALS, a serious neurological disorder that causes paralysis and death, despite doubts about its efficacy. of therapy.
The treatment, conceived a decade ago by two college students, was approved despite the fact that reviews by FDA reviewers concluded that there was not yet enough evidence that the drug could help patients live longer or slow down the rate of death. who lose functions such as muscle control, speech or breathing without help. However, the agency decided to give the drug the green light without waiting two years for the results of a larger clinical trial, arguing that the data shows that the treatment is safe and that patients feel desperate to have a disease. which usually causes death within 2 to 5 years.
The drug, whose scientific name is AMX0035, will be marketed as Relyvrio.
In a summary memorandum on the drug, the FDA wrote that there was “residual uncertainty about the evidence of efficacy,” but that “given the serious and life-threatening nature of ALS and the high unmet need, this level of uncertainty is acceptable in this case. The memorandum also asserted that the benefits outweigh the risks because the treatment “has no significant safety signals of concern.”
The approval comes after an impassioned campaign by patients and advocacy groups. In addition, doctors who treat ALS patients had urged the approval in a letter to the FDA and in testimony before an FDA advisory committee.
“In a job as difficult as ours, there is always the possibility of making a mistake; what we have to decide is what mistake we prefer to make, “said Richard Bedlack, director of the ALS clinic at Duke University, this month. “If AMX0035 is approved and we find out in two years that it doesn’t work, I doubt many will be upset because ALS sufferers were able to try something that was safe and looked promising in 2022.”
Bedlack added, “Can you imagine the mistake of not approving it and in two years getting confirmatory evidence that it did work? And realizing that all those patients already have major disabilities or even died when they didn’t have to? I don’t know how you could live with yourself if you make that mistake.”
Amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, is diagnosed in about 6,000 people worldwide each year. 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 disease progression by about 33 percent .
Relyvrio was conceived by Justin Klee and Joshua Cohen when they were undergraduates at Brown University. They proposed that the combination of taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a pediatric drug for a urea disorder, might protect neurons in the brain from damage in diseases such as ALS, by prevent dysfunction of two cell structures: the mitochondria and the endoplasmic reticulum. They later founded a small company in Massachusetts, Amylyx Pharmaceuticals.
When patients learned about the compound, some began to obtain the ingredients on their own from Amazon and other sources. In June, Canada became the first country to approve the treatment, with a special condition requiring Amylyx to later submit convincing evidence that it worked.
The drug, a bitter-tasting powder that is mixed with water and drunk or ingested through a tube, traveled an unusual and controversial path to approval. The FDA typically requires two conclusive clinical trials, usually phase 3, which are larger and more extensive than phase 2. For severe diseases with few treatments, the agency may accept one trial plus additional confirmatory data.
In the case of Relyvrio, the data comes only from a phase 2 trial in which 137 patients took the drug or a placebo, plus an extension study in which some patients were followed after the trial ended when intentionally taking the drug.
The phase 2 trial included patients who were considered to have rapidly progressing disease. Two-thirds of the participants received Relyvrio. Over 24 weeks, they had a 25 percent slower decline than participants who received a placebo, or 2.32 points less decline on a 48-point ALS scale that assesses 12 physical abilities such as walking, talking, swallowing, dressing, handwriting, and breathing.
The open-label extension study involved 90 such patients, including 34 in the placebo group, who started taking the drug about seven months after those who started from the beginning. Patients who received the treatment the longest took an average of about 6.5 months longer before they were hospitalized, put on a ventilator or died, Amylyx reported. The researchers later published another analysis that suggested additional benefit.
Initially, the FDA advised Amylyx not to apply for approval until the Phase 3 trial was completed in 2024.
However, Billy Dunn, director of the FDA’s office of neuroscience, told the advisory committee that “although some might argue that there is currently no substantial evidence” to justify approval, the agency should exercise “the broadest flexibility ” considering also the severity of the disease and the scarcity of available treatments.
Dunn posed a question to Amylyx: If the treatment were approved now and proved ineffective in the phase 3 trial, would the company remove the drug from the market to save the agency a lengthy withdrawal process? Klee said the company would agree to remove it.
This commitment from Amylyx, plus emotional testimonials from patients and physicians, convinced more members of the advisory committee at the September meeting, where the vote for approval was 7-2.