Food and Drug Administration advisers on Wednesday declined to endorse an experimental drug for patients with ALS, a setback for patients and advocacy groups eagerly pushing for the drug's approval.
The 4-6 vote capped off an all-day meeting where members of the agency’s Peripheral and Central Nervous System Drugs Advisory Committee weighed the drugmaker's request — along with the desires of many ALS patients — against the need for more robust data.
The close vote reflects the difficulty panel members faced in their decision. ALS, or amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a fatal disease with no cure. Many patients have said they are willing to accept the risk of taking a new drug if there's even a small chance it might help.
“I too have friends with ALS. It’s a terrible disease. Just like Alzheimer’s, there is no cure for these disorders, and they affect not only patients but the whole family,” said committee member Dr. Liana Apostolova, a neurologist and researcher at the Indiana University School of Medicine, after voting against the recommendation.
The decision will now go to the FDA, which isn't expected to make a final ruling for several months. The agency has faced pressure from advocacy groups to approve the drug quickly, despite concerns from regulators.
"I would not be surprised by a decision in either direction at this point," Holly Fernandez Lynch, an assistant professor of medical ethics at the University of Pennsylvania, said. "I think what's clear is that if the drug works, the benefits that it would offer are certainly meaningful to patients."
At issue was whether a single Phase 2 clinical trial of 137 patients showed strong-enough evidence that the drug, made by Cambridge, Massachusetts-based drugmaker Amylyx Pharmaceuticals, is effective.
The drug, known as AMX0035, aims to slow the progression of the disease by preventing special cells needed to walk, speak and eat from dying prematurely.
Data released by Amylyx showed that people who took the drug lived about six months longer compared to those who received a placebo.
But ultimately, the majority of the committee members said the data showing a slowing in the progression of the disease was not persuasive enough to recommend approval.
One factor members took issue with was the company’s own analysis of the trial data, which concluded that the drug reduced the risk of death by 44 percent over a three-year period.
“There were considerable concerns voiced by the FDA about the trial conduct and the interpretation of the results,” said committee member Dr. Bryan Traynor, a neurologist and a senior investigator at the National Institute on Aging, who voted against the recommendation.
Earlier in the day, FDA officials noted a number of patients dropped out of the trial, which could’ve skewed the results in favor of the drug.
They also pointed out problems with how the trial was conducted, such as the first 18 patients receiving the drug instead of being randomly selected to receive the drug or a placebo, which Amylyx attributed to shipping problems. Those patients were still included in the company’s application to the FDA.
On Monday, agency scientists released a critical review of the drug, saying in briefing documents that the company’s data on the drug “may not be sufficiently persuasive” to recommend approval.
During the meeting Wednesday, officials noted they usually require two large studies or one trial that has “very persuasive” evidence.
Amylyx is conducting a large Phase 3 clinical trial on the drug. Some panel members said they would prefer to wait for results from that trial before considering approval.
Representatives for Amylyx argued Wednesday that the data did show a clinical benefit to patients, a finding they said would be backed up by data from the ongoing Phase 3 trial and real-world data.
The benefit of the Amylyx drug is “clear,” said Dr. Sabrina Paganoni, a principal investigator of the smaller trial. “Delaying access is not a risk that we should take.”
'FDA has a choice to make'
The committee’s vote is only a recommendation, and the FDA doesn’t have to follow its advice. But the group’s lack of endorsement may weigh heavily on the agency, which has been under intense scrutiny from the scientific community over its handling of recent approvals.
Wednesday's meeting was the committee's first since it convened in November 2020 to consider approval of Aduhelm, an Alzheimer’s drug from the drugmaker Biogen. Aduhelm received full approval by the FDA in June, even though the advisory committee voted against its recommendation.
That decision was heavily criticized by outside experts at the time, and it is expected to face the same if it approves Amylyx’s drug.
If approved, advocacy groups say it would represent a major advancement for the roughly 30,000 people in the United States with ALS.
"FDA has a choice to make," Calaneet Balas, the president and CEO of The ALS Association, said in a statement following the vote. The group funded a portion of the Amylyx study, in part with money raised by the 2014 viral Ice Bucket Challenge.
"Whether it will approve a drug that has been proven safe that will help people living with ALS today, or whether it will delay approval and require more evidence while more people with ALS die," she said.
The committee meeting included a lengthy public comment period, where patients with ALS, along with advocacy groups and family members, expressed their desires to make the drug available, despite remaining questions.
Following the vote, committee member Dr. Kenneth Fischbeck acknowledged the moving testimony from patients and organizations.
“There’s no question the burdens of the disease,” said Fischbeck, an investigator at the National Institute of Neurological Disorders and Stroke.
Among the commenters was Laura Dalle Pazze, the CEO of I Am ALS, a patient advocacy group that has repeatedly urged the FDA to approve Amylyx’s drug as soon as possible.
Without approval, 20,000 patients currently diagnosed with ALS could die over the next three years, while an additional 20,000 will be newly diagnosed and slowly decline, she said.