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A new treatment for amyotrophic lateral sclerosis, or ALS, has been approved by the US Food and Drug Administration.
The FDA on Thursday announced approval of Relyvrio, developed by Amylyx Pharmaceuticals. The oral medication can be taken as a stand-alone therapy or with other treatments, according to the company, and 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 drug was effective before she changed her mind this month.
“There are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness that is greater than what might normally remain after a conclusion that substantial evidence of effectiveness has been shown,” 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 case.”
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.
“The goal of Amylyx is that everyone who is eligible for Relyvrio will have access to Relyvrio as quickly and efficiently as possible, as we know that people with ALS and their families don’t have time to wait,” they said. “As Amylyx works to launch Relyvrio, healthcare professionals will be able to immediately prescribe Relyvrio 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 as limited treatments are 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 and eventually impair the ability to speak, swallow, move and breathe.
“ALS is a terrible disease: rapidly deadly and really debilitating during the period from the first symptoms to death. FDA has approved a number of treatments, but they are minimally effective and certainly not a cure. And so there’s a huge unmet need in this disease area, which the FDA has recognized,” said Holly Fernandez Lynch, an assistant professor of medical ethics and health policy at the University of Pennsylvania.
Prior to the FDA decision, Lynch told CNN she would be “shocked” if the drug didn’t get approved, as the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee changed its opinion on the drug at a meeting this month. 7-2 for approval.
In November, Amylyx filed a drug application with the FDA for the drug, then called AMX0035, as an oral ALS treatment, seeking approval based on a Phase 2 study that enrolled 137 people with ALS who took either the drug or a placebo. received for 24 weeks. . The study was funded in part by a grant from the ALS Ice Bucket Challenge, the viral social media campaign that began in 2014 in which people threw 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 receiving the drug. Amylyx is now continuing to study its safety and efficacy in a phase 3 trial.
In March, the Advisory Committee on Peripheral and Central Nervous System Drugs voted 6 to 4 that a single Phase 2 study failed to conclude that the drug is effective in treating ALS.
“As for establishing the conclusion that it is effective, we were asked to look for substantial evidence with persuasion and robustness and I think this one trial doesn’t quite meet that bar,” Dr. Kenneth Fischbeck, one of the committee members and a researcher at the National Institutes of Health, said at the March meeting. Fischbeck added that he has cared for ALS patients.
A key difference between the FDA advisory committee meetings in March and September is that Amylyx indicated at the later meeting that if the drug was approved, but the results of the Phase 3 trial do not confirm the drug’s benefits, the company would consider withdrawing the drug from the market. said Lynch. However, she added that the company has not specifically said what it would consider a failure.
“So on the vote, the members of the advisory committee switched, and most of them said, ‘Yes, we are now convinced that this product should be approved.’ And when asked why they changed their minds, some said, ‘Well, the company said they’d pull out,’ she said. “And they were also convinced by the patient testimonials that they really want to try this drug.”
But in general, the FDA’s approval was based on Phase 2 trial data, which, Lynch said, can send a message to other drug companies that they don’t need robust Phase 3 trial data to get products to market.
Lynch said that while she understands why people with ALS want access to this promising drug, she worries that such a message could open the door wider for the approval of drugs that have not been proven to work. The FDA could later withdraw those products if necessary, she said, but doing so without a voluntary company agreement is “an enormous pain” and often requires a very lengthy process.
As for Relyvrio, some ALS advocacy groups — including the ALS Association — have been calling 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 must make a choice — whether to approve a drug that proven safe that it will help people with ALS today, or that it will delay approval and require more evidence, as more people with ALS die.”
“We cannot allow perfection to stand in the way of real progress in turning ALS from a deadly disease into a viable disease. The FDA’s own ALS guidelines recognize 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 do this urgently.”