Food and Drug Administration advisors on Wednesday refused to approve an experimental drug for patients with amyotrophic lateral sclerosis, a relapse for patients and advocacy groups eagerly pushing for approval of the drug.
The votes culminated 4-6 from the all-day meeting where members of the agency Peripheral and Central Nervous System Drug Advisory Committee Balance drugmaker demand—along with the desires of many ALS patients—against the need for more robust data.
The close vote reflects the difficulty the committee members faced in their decision. Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a fatal disease that has no cure. Many patients said they were willing to accept the risks of taking a new drug if there was a small chance it could help.
“I also 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 on the whole family.”
A decision will now go to the US Food and Drug Administration, which is not expected to issue a final ruling for several months. The agency faced pressure from advocacy groups to approve the drug quickly, despite regulators’ concerns.
“I wouldn’t be surprised by a decision either way at this point,” said Holly Fernandez-Lynch, associate professor of medical ethics at the University of Pennsylvania. “I think what’s clear is that if the drug works, the benefits that it will provide will certainly be meaningful to patients.”
The dispute has been whether a single Phase II clinical trial in 137 patients showed strong enough evidence that the drug, made by Cambridge, Massachusetts-based Amylyx Pharmaceuticals, was effective.
The drug, known as AMX0035, aims to slow the progression of the disease by preventing special cells needed to walk, talk and eat from dying prematurely.
Data from Amylyx showed that people who took the drug lived about six months longer than those who took the placebo.
But in the end, the majority of committee members said the data showing a slowing in the disease’s progression wasn’t convincing enough to recommend approval.
One factor raised by members was the company’s analysis of trial data, which concluded that the drug reduced the risk of death by 44 percent over a three-year period.
“There were significant concerns expressed by the FDA about conducting the trial and interpreting the results,” said panel member Dr. Brian Trainor, a neurologist and senior investigator at the National Institute on Aging, who voted against the recommendation.
Earlier in the day, Food and Drug Administration officials noted that a number of patients had withdrawn from the trial, which could skew results in favor of the drug.
They also cited problems with how the trial was conducted, such as the first 18 patients receiving the drug rather than being randomly selected to receive either the drug or a placebo, which they attributed to Amylyx’s shipping problems. These patients are still included in the company’s application to the Food and Drug Administration.
On Monday, agency scientists released a Critical review of the property, saying in a document briefing that the company’s statements on the property “may not be persuasive enough” to recommend approval.
During Wednesday’s meeting, officials indicated they usually need two large studies or one trial that contains “extremely convincing” evidence.
Amylyx is conducting a large phase III clinical trial of the drug. Some members of the committee said they would prefer to wait for the results of that trial before considering approval.
Amylyx representatives argued Wednesday that the data showed clinical benefit to patients, a finding they said will be supported by data from the ongoing Phase III trial and data from the real world.
Dr. Sabrina Pagani, lead researcher on the smaller trial, said the benefit of Amylyx was “obvious.” “Delaying arrival is not a risk we should take.”
“The Food and Drug Administration has a choice to make.”
The committee vote is just a recommendation, and the FDA doesn’t have to follow its advice. But the group’s lack of endorsement could weigh on the agency, which has come 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 disease drug from Biogen. Aduhelm received full approval by the Food and Drug Administration in June, although the advisory panel voted against its recommendation.
This decision was heavily criticized by outside experts at the time, and he is expected to face the same if he approves Amylyx.
If approved, advocacy groups say it would be a major advance for Nearly 30,000 people In the United States with ALS.
“The FDA has a choice to make,” Calanet Ballas, president and CEO of the ALS Association, said in a statement after the vote. The group funded the Amylyx study in part, in part with money raised by the viral 2014 Ice Bucket Challenge.
“Whether it will approve a drug that has been shown to be 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 an extended period of public comment, in which patients with ALS, along with advocacy groups and family members, expressed a desire to make the drug available, despite remaining questions.
After the vote, committee member Dr. Kenneth Fishbeck endorsed the influential testimony from patients and organizations.
“There is no question of disease burdens,” said Fischbeck, a researcher with the National Institute of Neurological Disorders and Stroke.
Among the commentators was Laura Dalle Pazze, CEO of I Am ALS, a patient advocacy group that has repeatedly urged the FDA to approve Amylyx as quickly as possible.
Without consent, 20,000 patients currently diagnosed with ALS could die within the next three years, while an additional 20,000 new ones will be diagnosed and slowly regress, she said.
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