Publisher Health

The Food and Drug Administration on Thursday approved an experimental treatment for A.L.S., a severe neurological disorder that causes paralysis and death, despite questions about the therapy’s effectiveness.

The treatment, conceived about a decade ago by two college students, was approved even though analyses by the F.D.A.’s reviewers concluded there was not yet sufficient evidence that the medication could help patients live longer or slow the rate at which they lose functions like muscle control, speaking or breathing without assistance. Nevertheless, the agency decided to greenlight the drug without waiting two years for results of a large clinical trial, citing data showing the treatment to be safe and the desperation of patients with a disease that often causes death within two-to-five years.

The drug, which has the scientific name AMX0035, will be marketed as Relyvrio.

In a summary memorandum about the drug the F.D.A. wrote that there was “residual uncertainty about the evidence of effectiveness,” but that “given the serious and life-threatening nature of A.L.S. and the substantial unmet need, this level of uncertainty is acceptable in this instance.” The memorandum also said that the benefits outweigh the risks because the treatment is “without any significant safety signals of concern.”

The approval follows an impassioned campaign by patients and advocacy groups. In addition, doctors who treat A.L.S. patients had urged approval in a letter to the F.D.A. and testimony and in testimony before an F.D.A. advisory committee.

“In your difficult job, there’s always going to be a chance of making a mistake; it comes down to which mistake you would rather make,” Dr. Richard Bedlack, director of the A.L.S. clinic at Duke University, testified this month. “To approve AMX0035 and find out in two years that it doesn’t work — I doubt many are going to be very angry because people with A.L.S. got to try something that was safe and appeared promising in 2022.”

But, he added, “Can you imagine the mistake of saying no and then getting confirmatory evidence in two years that this really did work? And realizing all those patients were much more disabled or even dead when they didn’t need to be? I don’t know how you’ll be able to live with yourself if you make that mistake.”

A.L.S., or amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, is diagnosed in about 6,000 people worldwide each year. There are only two other approved A.L.S. medications 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.

Relyvrio was conceived by Justin Klee and Joshua Cohen when they were undergraduate students at Brown University. They proposed that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for a pediatric urea disorder, could protect neurons in the brain from damage in diseases like A.L.S. by preventing dysfunction of two structures in cells: mitochondria and the endoplasmic reticulum. They later founded a small Massachusetts company, Amylyx Pharmaceuticals.

As patients learned about the compound, some began obtaining the ingredients on their own from Amazon and other sources. In June, Canada became the first country to approve the treatment, under a special condition requiring Amylyx to later provide better evidence that it worked. Advocacy groups predicted that some American patients would seek it from Canada, where it is marketed as Albrioza, if the F.D.A. didn’t approve it.

Amylyx did not immediately say what price it is considering for the treatment in the United States and has said the price is still being negotiated in Canada.

 “Amylyx’s goal is that every person who is eligible for Relyvrio will have access as quickly and efficiently as possible as we know people with A.L.S. and their families have no time to wait,” the company said in a statement after the F.D.A. announcement.

The medication, a bitter-tasting powder mixed with water and either drunk or ingested through a feeding tube, traveled an unusual and controversial path to approval. The F.D.A. typically requires two persuasive clinical trials, usually Phase 3 trials, which are larger and more extensive than Phase 2 studies. For serious diseases with few treatments, the agency can accept one trial plus additional confirmatory data.

For Relyvrio, the data comes only from one Phase 2 trial in which 137 patients took either 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 Phase 2 trial involved patients considered to have fast-progressing disease. Two-thirds of participants received Relyvrio. Over 24 weeks, they experienced a 25 percent slower decline than participants receiving placebo — declining 2.32 points less on a 48-point A.L.S. scale that rates 12 physical abilities, including walking, speaking, swallowing, dressing, handwriting and breathing.

The open-label extension study involved 90 of those patients, including 34 from the placebo group, who began taking the medication about seven months after those who received it from the beginning. Patients who received the treatment the longest had a median of about 6.5 months more time before being hospitalized, being put on a ventilator or dying, Amylyx reported. Researchers later published another analysis that suggested additional benefit.

The F.D.A. initially recommended that Amylyx not apply for approval until the Phase 3 trial was completed in 2024.

A.L.S. advocacy groups campaigned vehemently to persuade the F.D.A. to reconsider, especially after the agency’s controversial approval last year of the Alzheimer’s drug Aduhelm despite doubts about whether it worked. Soon after, F.D.A. officials began suggesting that Amylyx submit an application for approval using existing data.

In March, a committee of independent advisers to the F.D.A. voted by a narrow margin that the treatment had not yet been shown to be effective, a conclusion also reached by the F.D.A.’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 on Sept. 7. In a report presented there, agency reviewers said they also considered the new data insufficient.

But Dr. Billy Dunn, director of the F.D.A.’s office of neuroscience, told the advisory committee that “although some might reasonably argue that substantial evidence does not currently exist” to justify approval, the agency should exercise “the broadest flexibility” by also considering the seriousness of the disease and the dearth of available treatments.

Dr. Dunn posed a question to the company: If the treatment received approval now and was shown to be ineffective in the Phase 3 trial, would Amylyx voluntarily withdraw it from the market, saving the agency a lengthy recall process? Mr. Klee said the company would.

That commitment by Amylyx, plus emotional testimony from patients and doctors, persuaded more advisory committee members at the September meeting, where the vote favoring approval was seven to two.

One of those who voted against approval, Dr. Kenneth Fischbeck, a distinguished investigator for the National Institutes of Health, said the company could provide the therapy to patients for free while waiting for better evidence, but “I don’t think it’s met the standard of evidence to allow them to sell the drug.”

Mark Weston, a member of the advisory committee who has A.L.S., said he was disappointed that the new information the company presented wasn’t stronger. “I was hoping for something more,” he said. But Mr. Weston, who earlier in the meeting named A.L.S. patients who had died since the March hearing, said he voted for approval because “I can’t decouple my thoughts about that from my thoughts about the unmet need.”

That need for treatments was the overwhelming message of patients who testified. “Instead of thinking you are protecting me I want you to recommend approval so that I have the chance to live,” said Brian Wallach, 41, who co-founded “I AM ALS,” an advocacy group, in testimony mostly read by a friend because A.L.S. has profoundly damaged his ability to speak.

Gregory Canter, one of the clinical trial participants, said “the rate of my functional decline has slowed considerably” since beginning the drug over three years ago.

“A.L.S. is the basement; this starts us up the stairs,” Mr. Canter said. “It won’t get us to the top alone, but each step up is important to point us in the right direction.”

Calaneet Balas, president and chief executive of the A.L.S. Association, said in a statement that the F.D.A. decision was “a victory for the entire ALS community, which came together to advocate for early approval of AMX0035.” The association and other advocacy groups met with F.D.A. officials, submitted a petition with over 50,000 signatures and organized a campaign generating over 13,000 emails to the agency.

The A.L.S. Association contributed $2.2 million to the development and study of AMX0035, using money raised through the 2014 Ice Bucket Challenge. Amylyx agreed to use sales of the drug to repay 150 percent of the association’s grant to fund more research.