WASHINGTON (AP) — Federal health regulators remain unconvinced of the benefits of a closely watched experimental drug for the debilitating disease known as Lou Gehrig’s disease, even as they prepare to give his drugmaker a rare second opportunity to publicly advocate the treatment.
Amylyx Pharmaceuticals’ experimental drug has become a rallying cause for patients with this deadly neurodegenerative disease, their families, and members of Congress pushing the FDA to approve the drug.
But regulators said on Friday that the drugmaker’s new analyzes are not “sufficiently independent or convincing” to establish their effectiveness. The agency released its opinion ahead of a Wednesday meeting of its outside advisers, who will vote on whether to recommend approval.
In March, the same panel of neurological experts voted 6 to 4 that the company’s data failed to show a convincing benefit for ALS, or amyotrophic lateral sclerosis. It is extremely rare for the FDA to convene a second review meeting after its advisers have already voted.
The FDA will ask the panel to review several new statistical analyses, which the company says strengthen the case that its drug prolongs life and delays hospitalization and other serious complications. The FDA says experts can take into account “unmet need in ALS,” disease severity, and other factors specific to end-stage disease.
Elsewhere in its review, the FDA detailed the flexibility it can apply to drug approval decisions, particularly for life-threatening diseases, suggesting “there’s a chance the FDA is still looking for a way to fix it.” ‘endorse the product,’ wrote SVB analyst Marc Goodman. in a note to investors. It gives Amylyx a 50% chance of being approved.
ALS destroys the nerve cells needed to walk, talk, swallow and – eventually – breathe. There is no cure and most people die within three to five years.
The FDA review reflects some of the biggest questions facing the agency, including: How stringent should it be in enforcing drug approval standards for rare and life-threatening diseases? And what weight, if any, should be given to outside appeals by patients, advocates and their political allies?
Typically, FDA approval requires two large studies or one study with a “very persuasive” effect on survival.
The Amylyx data comes from a small, mid-stage trial that showed some benefit in slowing the disease, but was marred by missing data, implementation errors and other issues, according to the FDA reviewers.
Amylyx says follow-up data collected after the study ended shows that the drug’s lifespan is extended. When the company followed patients who continued to take the drug, they survived about 10 months longer than patients who never took the drug, according to new analysis from the company.
But the FDA said Friday that the new approach “suffers from the same interpretability issues” as the original Amylyx study and that the new analysis “is not independent data.”
The FDA does not publicly explain its rationale for holding meetings. But some outside analysts believe the agency hopes more outside input will strengthen its hand when it makes its final decision, expected by the end of the month.
Amylyx’s medicine is a combination of two older medicinal ingredients: a prescription drug for liver disorders and a dietary supplement associated with traditional Chinese medicine. The Cambridge, Mass., company patented the combination and claims the chemicals work together to protect cells from premature death. Its co-founders first discovered the suit as students at Brown University.
Some ALS patients already take both pills. FDA approval would likely force insurers to cover the treatment.
The FDA will again hear from patients and advocacy groups, such as I AM ALS, which has lobbied the FDA and Congress for more than two years to make the drug available. The group’s founder, Brian Wallach, said ALS patients, doctors and researchers believe the company’s data is worth trusting.
“Patients are doing their homework – we know this isn’t going to cure us,” said Wallach, who was diagnosed with ALS in 2017 and spoke through an interpreter. “But we also know it could keep us here until the next drug comes and that could be a cure.”
Wallach is currently taking the treatment part of Amylyx that is available as a dietary supplement.
Despite the negative FDA review, several outside developments could tip the FDA toward approval.
In June, Canadian regulators approved the drug for ALS patients, the first country to do so. The move puts FDA regulators in a “precarious position,” says bioethicist Holly Fernandez-Lynch.
“They generally like to be ahead when making approval decisions,” said Fernandez-Lynch, who teaches at the University of Pennsylvania. “They like to argue that they’re not a barrier to patients getting things that might help them.”
Amylyx shares fell more than 23% to close at $18 in trading on Friday.
The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.