The meeting was already unusual. Convened by the Food and Drug Administration Wednesday, a group of independent experts were, for a rare second time, gathering to review an experimental drug for ALS that has become the latest litmus test of the agency’s approval standards.
While the drug’s developer, Amylyx Pharmaceuticals, had positive clinical trial results in hand, FDA scientists had raised red flags about how that data was analyzed and, in March, the same expert panel voted against recommending it for approval.
Yet the agency had acknowledged the urgency of getting new medicines to ALS patients, who have few treatment options and face a fast-moving and fatal disease. Documents released ahead of Wednesday’s meeting also emphasized the FDA’s flexibility when considering drugs in this context.
The FDA’s position was made clearest by a 34-minute speech given at the start of the meeting by Billy Dunn, director of the regulator’s Office of Neuroscience and a key player in the agency’s controversial approval of another neurological disease drug, Biogen’s Alzheimer’s treatment Aduhelm.
“Our underlying legal authority is clear in not only allowing, but also endorsing and encouraging the application of regulatory flexibility in the setting of serious and life threatening diseases,” Dunn said at the meeting. “It is unquestionably relevant to ALS drug development in general and to our specific consideration of the data before us.”
Dunn noted how “regulatory flexibility played a direct role” in the past approvals for the two other drugs currently used to treat ALS. He then encouraged the committee members to consider, alongside the available data, a larger, currently enrolling trial of Amylyx’s drug that could provide confirmatory evidence of its benefit in just a few year’s time.
And, in a break for usual practice, he directly called on Amylyx to commit to withdrawing the drug from market should the FDA approve it and that confirmatory study fail.
Surprisingly, Amylyx’s founders did. “To be clear, if [the trial] is not successful, we will do what is right for patients, which includes voluntarily removing the product from the market,” said Justin Klee, Amylyx’s co-CEO and co-founder.
In a lengthy meeting that involved detailed discussion of clinical trial data, that commitment had an impact, helping shift the vote of at least one panelist and leading to a positive 7-2 recommendation that makes an FDA approval look more likely.
Bryan Traynor, a committee member and senior investigator at the National Institute on Aging, said he was “struck by the public statements” from Amylyx committing to withdraw the drug if that confirmatory study turns out negative. Traynor voted against Amylyx’s drug at the committee’s previous meeting in March, but voted in favor on Wednesday.
Liana Apostolova, a panelist and professor at the Indiana University School of Medicine, noted she was “reassured” by the possibility of a market withdrawal in that event.
Dunn’s comments also carried weight more broadly. Thomas Montine, the panel’s chair and a professor at Stanford University’s School of Medicine, cited them in justifying his decision to vote in favor, while Amylyx’s co-CEOs noted their impact as well.
“The commentary from Billy Dunn — really sharing the regulatory flexibility and applicable standards here for ALS — was also very important and was missing from the first panel,” said Justin Klee, in an interview with BioPharma Dive after the meeting.
Not everyone agreed, though, and one of the panelists who voted no, G. Caleb Alexander of Johns Hopkins Bloomberg School of Public Health, raised doubts about how effectively the FDA could enforce a drug’s withdrawal.
“The FDA, with all due respect, significantly understates the complexity and likelihood of their pulling a product from the market,” he said.
The agency is set to rule on approval of Amylyx’s drug, called AMX0035, by Sept. 29. Its decision will be closely watched by ALS patients and their families, who have urged the agency to live up to past commitments to take a more flexible approach in reviewing medicines for the neurological disease.
It will also be followed by the pharmaceutical industry, which is trying to divine the FDA’s standards for approving new drugs for brain disorders, especially after the intense debate surrounding the agency’s clearance of Aduhelm in Alzheimer’s.
Wall Street analysts who follow the sector took particular note of Dunn’s speech Wednesday. “We believe his risk-on tone and emphasis on considering the context of data, coupled with what appears to be more openness and flexibility, are likely to create a more favorable overall environment across relevant FDA divisions,” wrote Brian Abrahams, an analyst at RBC Capital Markets, in a note to clients.
Jacob Bell contributed reporting
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