FDA panel backs much-debated ALS drug in rare second review

A panel of federal health advisers voted Wednesday to recommend approval of an experimental drug to treat Lou Gehrig’s disease, a notable change for the hotly debated drug that was previously rejected by the same group.

Food and Drug Administration advisers voted 7-2 that the data from Amylyx Pharma warranted approval, despite ongoing concerns about the robustness and reliability of the company’s only study. The vote is non-binding and the FDA will make its final decision by the end of the month.

Despite a negative review published by internal FDA scientists before the meeting, most outside panelists said Amylyx had presented enough evidence to suggest the drug is likely helping patients live longer.

“Depriving ALS patients of a drug that might work is probably not something I would be very comfortable with,” said Liana Apostolova, MD, of the Indiana University School of Medicine, who voted in favor of the approval. “In the previous meeting it was not so clear and it is still questionable.”

Amylyx also appeared to benefit from an unusual exchange in which a company executive, at the FDA’s request, vowed to withdraw the drug from the market if its benefits are not confirmed by a large ongoing study.

“I am somewhat sure that if an approval is issued, it can be withdrawn in the future,” Apostolova said.

Wednesday’s vote concluded a rare second meeting to review several new statistical analyzes submitted by Amylyx in support of the treatment’s benefit in slowing disease and prolonging life. The same group of neurology experts narrowly voted against the drug in March, due to concerns about lack of data and implementation errors in the company’s study.

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

THE A patients and their families rallied behind the Amylyx drug, launching an aggressive lobbying campaign and enlisting members of Congress to pressure the FDA for approval.

The ALS drug review is being 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, the FDA’s neurology review chief, opened the meeting by detailing “concerns and limitations” with 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 study of Amylyx being conducted in the US 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 agreed to withdraw its drug if the ongoing 600-patient trial doesn’t show a benefit. He then asked the company’s co-founders to publicly commit to that step, and Amylyx co-CEO Justin Klee said the company would voluntarily withdraw its drug in that scenario.

The FDA has the power to force companies to remove drugs from the market, though it’s usually quicker if drugmakers take that step voluntarily. In cases where companies resist removal, the regulatory process can drag on for years.

“I think the FDA, with all due respect, significantly underestimates the complexity and the likelihood that they will pull the product from the market,” said Dr. Caleb Alexander of Johns Hopkins University, one of two panelists who voted against the drug. .

Amylyx conducted a small, mid-stage trial of its drug that showed some benefit in slowing disease, but was plagued by missing data and other problems, according to FDA reviewers.

“The bottom line, for a single study, is borderline and not very statistically persuasive,” FDA statistician Tristan Massie told panelists.

The Cambridge, Massachusetts company says follow-up data collected after the study concluded showed the drug’s shelf life was prolonged. Patients who continued to take the drug survived about 10 months longer than patients who never took it, according to a new analysis from the company.

Panelists who favored the drug cited the data, along with the drug’s mild side effects, to suggest there would be little downside to patients, even if it doesn’t ultimately delay 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 families told aides they supported approval. The agency has also received more than 1,200 written comments, mostly from ALS patient advocates.

“I’m asking you to approve it because I know it works. It’s lengthening my life and I want that 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 medicine comes in a powder form that combines two older medicines: a prescription drug for liver disorders and a dietary supplement used in traditional Chinese medicine.

Hanging over the review is Controversial FDA approval of Alzheimer’s drug Aduhelm last year, which was reviewed by scientists from the same agency and outside advisers.

In that case, the FDA overrode the overwhelmingly negative vote of its outside advisers, three of whom resigned over the decision. The agency’s approval, which followed irregular meetings with drugmaker Biogen, is under investigation by Congress and federal inspectors.

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