Relyvrio: ALS drug gets FDA approval despite uncertainty over efficacy


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

The FDA on Thursday announced the approval of Relyvrio, made by Amylyx Pharmaceuticals. The oral drug can be taken as a stand-alone treatment or in combination with other treatments and has been shown to slow the progression of the disease, according to the company.

But there is still some uncertainty about the drug’s effectiveness: Amylyx’s submission for approval was based on data from a small Phase 2 trial, and the FDA’s own advisory committee voted this spring that the data did not show the drug was effective. this month’s idea.

“There are limitations to these findings that result in some degree of uncertainty regarding the evidence of efficacy beyond what would remain after a conclusion in which substantial evidence of efficacy has been demonstrated,” the FDA’s summary memorandum of the approval said. But “given the serious and life-threatening nature of ALS and the significant unmet need, the level of uncertainty in this case is reasonable.”

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

“Amylyx’s goal is for everyone eligible for Relyvrio to get access as quickly and efficiently as possible, because ALS patients and their families don’t have time to wait,” they said. “As Amylyx works to launch Relyvrio, healthcare providers will be able to immediately write prescriptions for Relyvrio by enrolling their patients in our comprehensive support program we have in place.”

Patients and some advocacy groups urged the FDA to approve the drug because limited treatments are available for ALS, and the agency gave it priority review in December.

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

“ALS is a terrible disease: rapidly fatal and truly debilitating from initial symptoms to death. The FDA has approved several treatments, but they are minimally effective and certainly not a cure. So there is a vast unmet need in this disease area that the FDA recognizes.” said Holly Fernandez Lynch, associate professor of medical ethics and health policy at the University of Pennsylvania.

Before the FDA’s decision, Lynch told CNN he would be “shocked” if the drug is not approved because the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee changed its opinion on the drug during a vote at a meeting this month. 7-2 in favor of confirmation.

In November, Amylyx submitted a drug application to the FDA for the drug, then called AMX0035, seeking approval based on a Phase 2 trial involving 137 people with ALS who received either the drug or a placebo for 24 weeks. . The research was funded in part by the ALS Ice Bucket Challenge, a 2014 viral social media campaign in which people doused themselves with ice water to raise awareness and money for ALS.

The trial also showed that the drug was generally well tolerated, but there was a higher incidence of gastrointestinal events in the drug-treated group. 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 6-4 that a Phase 2 trial did not find the drug effective in treating ALS.

“In terms of concluding that it’s effective, we were required to look for substantial evidence with credibility and robustness, and I don’t think this one trial quite fits that framework,” said Dr. Kenneth Fishback, one of the committee members. The investigator of the National Institute of Health said at the March meeting. Fischbeck added that he cared for ALS patients.

The main difference between the March and September meetings of the FDA advisory committee is that at the latter meeting, Amylyx indicated that if the drug is approved but its Phase 3 trial results fail to confirm the drug’s benefits, the company will consider taking the drug off the market. Lynch said. However, he added that the company did not specify what it would consider a failure.

“So during the vote, the members of the advisory committee changed, and many of them said, “Yes, we now feel confident that this product should be approved.” When asked why they changed their minds, some said, “Well, the company said they were going to back out.” “And they were convinced by the patients’ testimony that they wanted to try this drug.”

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

Lynch said that while he understands why ALS patients want access to this promising drug, he worries that such a message could open the door wider to the approval of unproven drugs. The FDA said it could later withdraw these products if necessary, but doing so without a 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 pushing for its approval for several months. After an 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, “The FDA has a choice — whether to approve the drug. It will help people living with ALS today. or will more people with ALS delay confirmation and require more evidence when they die?

“We cannot allow perfection to prevent real progress toward transforming ALS from a fatal disease to a livable one. The FDA’s ALS Guidance recognizes that people with ALS are willing to accept greater risk to gain some benefit,” Balas said. “People with ALS and their loved ones deserve better, and the FDA has the tools to do that urgently.”

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