A new treatment for amyotrophic lateral sclerosis, or ALS, has been approved by the US Food and Drug Administration.
The FDA announced the approval of Relyvrio, developed by Amylyx Pharmaceuticals, on Thursday. The oral medication can be taken as a stand-alone therapy or with other treatments, according to the company, and it has been shown to slow disease progression.
But there is still some uncertainty about the drug’s effectiveness: Amylyx’s submission for approval is based on data from a small phase 2 study, and the FDA’s own advisory committee first voted this spring that the data did not show the drug was effective, before changing its meaning this month.
“There are limitations to these findings that result in a degree of residual uncertainty about the evidence of efficacy that exceeds what might ordinarily remain after a conclusion that substantial evidence of efficacy has been demonstrated,” an FDA summary memorandum on the approval said. But “given the serious and life-threatening nature of ALS and the significant unmet need, this level of uncertainty is acceptable in this case.”
The approval is the first in the United States for Amylyx, CEOs Josh Cohen and Justin Klee said in a statement, and “is an exciting milestone” for the ALS community.
“Amylyx’s goal is that every person eligible for Relyvrio will have access as quickly and efficiently as possible, as we know that people with ALS and their families do not have time to wait,” they said. “As Amylyx works to launch Relyvrio, healthcare providers will be able to write prescriptions for Relyvrio immediately by enrolling their patients in our comprehensive support program that we are implementing.”
Patients and some advocacy groups had urged the FDA to approve the drug, since 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 is a neurodegenerative disease that causes muscles to weaken, eventually affecting the ability to speak, swallow, move and breathe.
“ALS is a terrible disease: rapidly fatal and truly devastating in the period from the first symptoms to death. The FDA has approved a couple of treatments, but they are minimally effective and absolutely no cure. And so, there is a huge unmet need in this area of the disease , which the FDA has recognized, says Holly Fernandez Lynch, assistant professor of medical ethics and health policy at the University of Pennsylvania.
Ahead of the FDA decision, Lynch told CNN she would be “shocked” if the drug was not approved because the FDA’s Peripheral and Central Nervous System Advisory Committee made a shift in its opinion on 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 drug, then called AMX0035, as an oral ALS treatment, seeking approval based on a phase 2 study 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 and involved people dumping buckets of ice water over themselves to raise awareness and money for ALS.
The trial also showed that the drug was generally well tolerated, but there was a greater frequency of gastrointestinal events in the group receiving the medication. Amylyx is now continuing to study safety and efficacy in a phase 3 study.
In March, the Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that a single phase 2 study did not establish the conclusion that the drug is effective in treating ALS.
“When it comes to 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 threshold,” Dr. Kenneth Fischbeck, one of the committee’s members and an investigator at the National Institutes of Health, said at the March meeting. Fischbeck added that he has cared for ALS patients.
An important difference between the March and September FDA advisory committee meetings is that in the later meeting, Amylyx indicated that if the drug was approved, but the results of the phase 3 trials did not confirm the benefits of the drug, the company would consider withdrawing the drug from the market. , Lynch said. However, she added that the company did not say specifically what it would consider a failure.
“Then at the vote, the advisory committee members switched, and most of them said, “Yes, we’re now convinced that this product should be approved.” And when asked why they changed their minds, some of them said, ‘Well, the company said that they would withdraw,'” she said. “And they were also convinced by the patients’ testimony that they would very much like to try this drug.”
But overall, the FDA’s approval was based on Phase 2 study data, which, Lynch said, could send a message to other pharmaceutical companies that they don’t need robust Phase 3 study data to get products to market.
Lynch said that while she understands why people with ALS want access to this promising drug, she is concerned that such a message could open the door wider to the approval of drugs that have not been proven to work. The FDA can later withdraw these products if necessary, she said, but doing so without voluntary company agreement is “a huge pain” and often requires a very long process.
As for Relyvrio, some ALS advocacy groups — including the ALS Association — have been seeking approval for months. After the FDA’s 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 “the FDA has a choice to make — whether to 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 let perfection stand in the way of real progress toward turning ALS from a fatal disease into a livable disease. The FDA’s own ALS guidance recognizes that people with ALS are willing to accept greater risk for the possibility of some benefit,” said Balas. “People with ALS and their loved ones deserve better, and the FDA has the tools to achieve this with urgency.”