FDA panel backs highly controversial ALS drug in rare 2nd review

WASHINGTON (AP) — A panel of federal health advisers voted Wednesday to recommend approval of an experimental drug to treat Lou Gehrig’s disease, a remarkable turnaround for the highly controversial drug which was previously rejected by the same group earlier this year.

Food and Drug Administration advisers voted 7 to 2 that Amylyx Pharma’s data warranted approval, despite hours of debate over the strength and reliability of the company’s only study. The FDA is not bound to follow the panel’s advice, but its positive recommendation suggests approval is likely later this month.

The FDA has only approved two therapies for the disease, amyotrophic lateral sclerosis, or ALS, which destroys nerve cells needed for basic functions like walking, talking and swallowing.

ALS patients and their families have rallied behind Amylyx’s drug, launching a aggressive lobbying campaign and enlisting members of Congress to push the FDA into granting approval.

Despite a negative review posted by internal FDA scientists ahead of the meeting, the majority of outside panelists said Amylyx presented enough evidence to suggest the drug helps patients live longer. The same group of neurology experts closely voted against drugs in marchdue to concerns about missing data and other issues in the company’s study.

“Depriving ALS patients of a drug that might work is probably not something I would feel very comfortable with,” said Dr Liana Apostolova of the University of Indiana, which voted for its approval. “In the previous meeting it wasn’t so clear and it’s still debatable.”

Amylyx also appeared to benefit from an unusual exchange in which a company executive – at the request of the FDA – pledged to pull the drug from the market if its benefits are not confirmed by a large ongoing study.

“I am somewhat assured that if an approval is issued, it can be withdrawn in the future,” Apostolova noted.

Wednesday’s vote concluded a rare second meeting to review several new statistical analyzes submitted by Amylyx in support of the treatment’s benefits for slowing disease and extending life.

The review of ALS drugs is closely watched as an indicator of the FDA’s flexibility in reviewing experimental drugs for the terminally ill and its ability to withstand outside pressure.

Dr. Billy Dunn, FDA Neurology Review Lead, opened the meeting by detailing the “concerns and limitations” of the Amylyx data, while emphasizing the need for new treatment options.

“We are very sensitive to the urgent need to develop new treatments for ALS,” Dunn said.

Dunn also noted that a larger Amylyx study conducted in the United States and Europe could provide “more definitive results” by 2024.

In a highly unusual move, Dunn suggested the agency might be more willing to approve the drug if Amylyx committed to withdrawing its drug if the ongoing 600-patient trial did not show benefit. He then called on the company’s co-founders to publicly commit to the move, and Amylyx co-CEO Justin Klee said the company would voluntarily withdraw its drug in this scenario.

The FDA has the power to force companies to pull drugs off the market, though it’s usually faster if drugmakers voluntarily take this step. In cases where companies resist withdrawal, the regulatory process can drag on for years.

“I think the FDA – with all due respect – is grossly underestimating the complexity and the likelihood of them removing the product from the market,” said Dr. Caleb Alexander of Johns Hopkins University, the one of two panelists who voted against the drug.

Amylyx ran a small, mid-stage trial of its drug that showed some benefit in slowing the disease, but it was plagued with missing data and other issues, according to FDA reviewers.

“The end result – for a single study – is borderline and not very convincing statistically,” FDA statistician Tristan Massie told panelists.

The Cambridge, Mass.-based company says follow-up data collected after the study ended showed that the drug’s lifespan was extended. Patients who continued taking the drug survived around 10 months longer than patients who never took the drug, according to a new analysis from the company.

Panelists in favor of the drug cited this data, along with the drug’s mild side effects, to suggest there would be little harm to patients, even if it ultimately does not slow ALS.

“The drug is not harmful – it appears to have a benefit – there is no safety signal here,” said Dean Follmann, a biostatistician at the National Institutes of Health.

Earlier Wednesday, more than 20 ALS researchers, patients and family members told advisers they supported approval. The agency also received more than 1,200 written comments, largely from ALS patient advocates.

“I’m asking you to approve it because I know it works. It prolongs my life and I wish it for others,” said Greg Canter, who was diagnosed with ALS in 2018 and participated in the Amylyx study. He credits the drug with improving his lung capacity and slowing his functional decline.

Amylyx’s drug comes in a powder form that combines two older drugs: a prescription drug for liver disorders and a dietary supplement used in traditional Chinese medicine.

The controversial FDA approval of Alzheimer’s disease drug Aduhelm last year, which was reviewed by the same agency scientists and outside advisers.

In this case, the FDA ignored the vast majority negative vote by his outside advisers, three of whom resigned following this decision. The agency’s approval — which followed irregular meetings with drugmaker Biogen — is being investigated by Congress and federal inspectors.


Follow Matthew Perrone on Twitter: @AP_FDAwriter


The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.

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