FDA advisory vote casts pall over the future of Amylyx’s experimental ALS drug

A panel of neurologists voted against recommending approval, despite pleas from patients.

Amylyx co-founders Justin Klee, left, and Joshua Cohen are also the company's co-chief executives.CODY O'LUGHLIN/NYT

An independent panel of neurologists that advises the US Food and Drug Administration voted 6 to 4 Wednesday against recommending the agency approve a Cambridge company’s experimental therapy for amyotrophic lateral sclerosis, also called Lou Gehrig’s disease.

The drug, produced by Amylyx Pharmaceuticals, slowed progression of the disease by 25 percent and improved survival a median of 4.8 months compared with placebo, according the the company. In what many described a difficult decision, a narrow majority of panel members were not convinced that Amylyx’s small clinical trial, which involved 137 ALS patients, proved the drug’s effectiveness.

There is no cure for the devastating disease, and people often survive only a few years after diagnosis. Some existing drugs can slightly slow the progression of the disease and delay death by a few months.

The drug is a combination of two molecules ― sodium phenylbutyrate and taurursodiol ― which Amylyx believes reduce stress and improve energy production in nerve cells, which break down during the disease.

During a full day meeting, scientists from Amylyx and FDA presented conflicting interpretations of data from the company’s trial. Patients participating in it got either the the drug or a placebo for 24 weeks.

Amylyx believes the drug makes a meaningful difference in the lives of people with ALS. Dr. Sabrina Paganoni, a physician who works with ALS patients at Mass General Hospital and was the coleader of Amylyx’s trial, said that the first treatments developed for HIV and multiple sclerosis were not curative, but they bought time for patients.

“I know this drug does not stop or reverse the disease. Nothing does,” she said during the FDA meeting held online. But she is convinced that the drug is safe and that its benefit is clear. “To me, the greatest risk comes from delaying access to treatment that has demonstrated significant benefit,” Paganoni said.

Dr. Teresa Buracchio, a director of neurology at the FDA, opened the meeting by acknowledging the need for new ALS drugs while also making clear the agency’s concern’s about the effectiveness of the drug and the rigor of the company’s trial.

“I want to assure both the ALS community and the committee that we at the FDA have heard the concerns of the ALS community and are responsive to them,” she said.

Dr. Emily Freilich, a neurologist at the FDA, detailed a bevy of concerns the agency had with Amylyx’s trial. The study was small and other drugs that people took during it may have skewed the results. The agency disagreed with the Amylyx’s statistical analysis. And since the drug has a bitter taste and can cause gastrointestinal side effects, people may have been able to tell that they got the drug instead of the placebo, potentially effecting the results, Freilich said.

The meeting included a lengthy public hearing that was overwhelmingly dominated by ALS patients and their family members. They pleaded with the FDA to approve the drug.

One man living with ALS said that although regulators may consider the drug’s effects modest, extending life by six months is significant for someone who is told they only have a couple of years to live. “Even though this treatment may not be the cure we’re all hoping for, it will get us a step closer to living with ALS and not just dying from it,” he said.

Another patient who was in the Amylyx trial and still takes the drug through a compassionate use program, shared pictures of himself playing hockey with his grandchildren and going on family vacations. “I believe every ALS patient should have the opportunity to have [the drug] because I see real benefits,” he said.

Physicians who treat patients with ALS also testified in favor of the drug, including Dr. James Berry, director of the ALS clinic at Mass General Hospital. He believes the therapy “measured up” in Amylyx’s clinical trial, which he co-led at the hospital. “Inaction today will delay a decision by years, during which a generation of people with ALS will die,” he said.

Few people opposed the drug during the hearing. Michael Abrams, a researcher at the progressive consumer think tank Public Citizen, and Diana Zuckerman, president of the National Center for Health Research, both independently argued that the current data do not support approval.

Neurologists who voted for and against approving the drug alike described their decision as difficult. The vote is a recommendation and is not legally binding. The FDA is expected to make its decision on the drug by late June. The agency usually, but not always, agrees with its advisory panels. Last summer, the FDA approved Cambridge biotech Biogen’s Alzheimer’s drug, Aduhelm, even though the advisory committee recommended against it.

Amylyx is currently testing the drug in a larger study that will eventually include 600 people. Topline results are expected in 2024. Paganoni, the Mass General physician, said that waiting for those results would force patients to wait at least two or three years for the treatment.