ALS drug gets FDA approval despite uncertainty about effectiveness

 (CNN) — A new treatment for amyotrophic lateral sclerosis, or ALS, has been approved by the US Food and Drug Administration.

The FDA announced approval of Relyvrio, developed by Amylyx Pharmaceuticals, on Thursday. The oral medication can be taken as a standalone therapy or with other treatments, according to the company, and it has been shown to slow disease progression.

But there’s still some uncertainty about the drug’s efficacy: Amylyx’s submission for approval is based on data from a small Phase 2 trial, and the FDA’s own advisory committee initially voted this spring that the data didn’t show that the drug was effective, before changing its opinion this month.

“There are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness that exceeds that which might typically remain following a conclusion that substantial evidence of effectiveness has been demonstrated,” says an FDA summary memorandum on the approval. But “given the serious and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this instance.”

The approval is the first in the US for Amylyx, CEOs Josh Cohen and Justin Klee said in a statement, and “is an exciting milestone” for the ALS community.

“Amylyx’ goal is that every person who is eligible for Relyvrio will have access as quickly and efficiently as possible as we know people with ALS and their families have no time to wait,” they said. “While Amylyx is working on launching Relyvrio, healthcare professionals will be able to write prescriptions for Relyvrio immediately by enrolling their patients into our comprehensive support program that we are implementing.”

Patients and some advocacy groups had urged the FDA to approve the drug, as there are limited treatments available for ALS, and the agency granted priority review in December.

ALS, also known as Lou Gehrig’s disease, affects as many as 30,000 people in the United States. It’s a neurodegenerative disease that causes muscles to weaken, eventually affecting the ability to speak, swallow, move and breathe.

“ALS is a horrific disease: rapidly fatal and really debilitating during the period from initial symptoms to death. FDA has approved a couple of treatments, but they are minimally effective and certainly not a cure. And so, there’s a vast unmet need in this disease area, which FDA has acknowledged,” said Holly Fernandez Lynch, an assistant professor of medical ethics and health policy at the University of Pennsylvania.

Ahead of the FDA decision, Lynch told CNN that she would be “shocked” if the drug did not get approved because the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee made a shift in its opinion of the drug at a meeting this month, voting 7-2 in favor of approval.

In November, Amylyx submitted a drug application to the FDA for the medication, then called AMX0035, as an oral ALS treatment, seeking approval based on a Phase 2 trial that included 137 people with ALS who received either the drug or a placebo for 24 weeks. The study was funded in part by a grant from the ALS Ice Bucket Challenge, the viral social media campaign that started in 2014 involving people dumping buckets of ice water over themselves to raise awareness and money around ALS.

The trial also showed that the drug was generally well-tolerated, but there was a greater frequency of gastrointestinal events in the group getting the medication. Amylyx is now continuing to study its safety and efficacy in a Phase 3 trial.

In March, the Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that a single Phase 2 trial did not establish the conclusion that the drug is effective in treating ALS.

“In terms of establishing the conclusion that it’s effective, we were asked to look for substantial evidence with persuasiveness and robustness and I think this one trial doesn’t quite meet that bar,” Dr. Kenneth Fischbeck, one of the committee members and an investigator at the National Institutes of Health, said at the March meeting. Fischbeck added that he has cared for ALS patients.

One key difference between the FDA advisory committee’s March and September meetings is that in the later meeting, Amylyx indicated that if the drug was approved but its Phase 3 trial results fail to confirm the drug’s benefits, the company would consider withdrawing the drug from the market, Lynch said. She added, however, that the company didn’t say specifically what it would view as a failure.

“So at the vote, the advisory committee members switched, and most of them said, ‘Yes, we are now convinced that this product should be approved.’ And when they were asked why they changed their minds, some of them said, ‘Well, the company said they would withdraw,’ ” she said. “And they were also convinced by patients’ testimonies that they very much want to try this drug.”

But overall, the FDA’s approval was based on Phase 2 trial data, which, Lynch said, may send a message to other pharmaceutical companies that they don’t need robust Phase 3 trial data to get products on the market.

Lynch said that although she understands why people with ALS want access to this promising drug, she has concerns that such a message could open the door more broadly to the approval of medications that have not been proved to work. The FDA could later withdraw those products if needed, she said, but doing so without voluntary company agreement is “a huge pain” and often requires a very lengthy process.

As for Relyvrio, some ALS advocacy groups — including the ALS Association — have been rooting for its approval for several months. After the FDA advisory committee meeting in March, when the panel initially voted against the drug, Calaneet Balas, president and CEO of the ALS Association, said in a statement that “FDA has a choice to make — whether it will approve a drug that has been proven safe that will help people living with ALS today, or whether it will delay approval and require more evidence while more people with ALS die.”

“We cannot allow perfection to stand in the way of real progress toward turning ALS from a fatal disease into a livable one. The FDA’s own ALS Guidance acknowledges that people with ALS are willing to accept greater risk for the possibility of some benefit,” Balas said. “People with ALS and their loved ones deserve better and the FDA has the tools to accomplish this with urgency.”