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In a surprise reversal, FDA committee recommends ALS drug by Cambridge company

The FDA is expected to make a final decision on the drug, from Cambridge-based Amylyx Pharmaceuticals, by the end of the month

A sign for the Food and Drug Administration is seen in Silver Spring, Md., on Thursday, Dec. 10, 2020.Manuel Balce Ceneta/Associated Press

Amylyx Pharmaceuticals was dealt a surprising boost Wednesday evening in its effort to commercialize a drug for amyotrophic lateral sclerosis, a fatal neurological disease. The Food and Drug Administration’s committee of neurology experts voted 7 to 2 in favor of the Cambridge company’s drug.

The meeting marked the second time this year that the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, a group of independent medical experts, convened to discuss Amylyx’s drug. In March, the committee voted 6 to 4 against approval.

The unexpected reversal, which was partly due to pleas from patients and their families and partly due to additional data presented by Amylyx, bodes well for the company. But it is only a recommendation. FDA regulators have the final say in authorizing or rejecting the drug by the end of the month.


“I thought it was the right decision, although I expected the vote would be a little closer,” said Dr. Merit E. Cudkowicz, director of the ALS center at Massachusetts General Hospital and co-principal investigator of Amylyx’s clinical trial. “We don’t have any other drug that slows progression, prolongs survival, and is safe,” she added. “I am hopeful that the FDA will approve it, and I think this sends a positive message.”

ALS, commonly called Lou Gehrig’s disease, is caused by the death of nerve cells which leads to progressive muscle weakness, paralysis, and death. Some treatments are thought to slow the progression of the disease by a few months, but there is no cure and most people die within 3 to 5 years of diagnosis.

Amylyx has developed a combination of two molecules — sodium phenylbutyrate and taurursodiol — that it believes helps delay the death of nerve cells. An intermediate clinical trial of 137 people with ALS found that its drug prolonged survival by a median 4.8 months compared to placebo.


“It’s not a cure. And in terms of survival, it’s a baby step,” said Dr. Robert H. Brown, an ALS researcher at UMass Chan Medical School. “Nonetheless, for those who have the disease, that’s very important.”

An advanced clinical trial testing the drug in about 600 people is underway with results expected as soon as 2024.

“If it works but we wait two or three years to get a definitive answer, then we will have lost the opportunity to treat a large number of patients,” Brown said.

The company decided to ask the FDA to approve the drug based on data from its intermediate trial. In March, the FDA’s advisory committee narrowly concluded that evidence for the drug’s effectiveness wasn’t strong enough to justify approval. FDA scientists also voiced skepticism about Amylyx’s interpretations of its data.

Amylyx co-founders Joshua Cohen, left, and Justin Klee in Cambridge, Mass. in 2018.Associated Press

Nonetheless, the agency made the unusual decision to convene another meeting, giving Amylyx a second chance to pitch its therapy.

During the Wednesday meeting, Amylyx said its drug lowered levels of a spinal fluid biomarker associated with ALS and Alzheimer’s disease. The company also presented new analyses of its clinical data suggesting that its therapy helps people with ALS live up to 11 months longer when compared with historical data about the progression of the disease.

The FDA said at the meeting that Amylyx’s biomarker data was not clearly linked to clinical benefit for ALS patients. The agency also seemed unconvinced by the company’s survival analyses, which it characterized as new interpretations of old data.


Dr. G. Caleb Alexander, professor of epidemiology and medicine at Johns Hopkins Bloomberg School of Public Health, voted against the drug, citing “many non-trivial scientific concerns” about how Amylyx’s clinical trial was conducted and how its data were analyzed. Waiting for the results of the company’s ongoing clinical trial will hopefully provide more firm answers about whether the drug works or not, he added.

Dr. Robert C. Alexander, chief scientific officer of the Alzheimer’s Prevention Institute, voted in favor of the drug, reversing his March vote against the drug. Although he said it was “a close call,” the testimony of ALS patients and family, as well as the additional evidence for a survival benefit from Amylyx’s therapy, made him change his mind.

Canadian regulators approved Amylyx’s drug in June with the condition that the company submit data from its ongoing Phase 3 clinical study, which may wrap up in 2024. The FDA may opt for a similar approach, although experts note that the agency has a poor track record of removing ineffective drugs from the market once they’ve been approved.

Brown was excited and surprised by the largely positive margin of the vote, but he said it’s hard to predict which way the FDA’s decision will land.

The agency decided to approve Biogen’s drug for Alzheimer’s last summer under the condition that the company continue testing it in clinical trials. That decision had the potential to benefit patients, Brown said, but it backfired on the company with an avalanche of negative publicity for the drug, which many neurologists said didn’t work and Medicare declined to cover.


“I wonder if that will influence the appetite FDA now has for doing something like that again,” Brown said.

Ryan Cross can be reached at Follow him on Twitter @RLCscienceboss.