Amylyx Pharmaceuticals Inc.’s controversial treatment for amyotrophic lateral sclerosis won the support of a panel of U.S. regulatory advisers, putting the product on track for likely clearance.
During a rare second panel meeting on Wednesday, the Food and Drug Administration’s peripheral and central nervous system drugs advisory committee voted 7-2 to back approval of the treatment. Trading in the shares was halted.
During an initial meeting in March, FDA advisers found that data from Amylyx’s relatively small initial trial was insufficient to prove that AMX0035 slowed ALS progression. The negative decision put the FDA in a bind, as the agency, under pressure from disease activists, has promised to exercise flexibility in approving drugs for dire illnesses such as ALS, given the urgent need for better treatments.
New data from Amylyx “is not unequivocally persuasive, but nonetheless is quite reassuring,” said Liana Apostolova of Indiana University School of Medicine, who voted in favor of the drug this time after voting against it in March. She took into account the fact that ALS “is a horrific disorder, it is a death sentence.”
At the Wednesday meeting, Billy Dunn, the FDA’s director of the office of neuroscience, acknowledged the “urgent need” for new ALS treatments and said several times that “we haven’t made any final decisions on the approvability of this application.”
‘Broadest flexibility’
The agency has determined that it is appropriate to exercise “the broadest flexibility” in applying the statuary standards, he said. “The procedures reflect the recognition that physicians and patients are generally willing to accept greater risks or side effects from products that treat life-threatening or severely debilitating illnesses than they would from products that treat less serious illnesses.”
If the drug is approved now, and the company’s follow-up clinical trial is unsuccessful, Amylyx will voluntarily remove the product from the market, co-Chief Executive Officer Justin Klee said at the hearing.
AMX0035 combines two compounds, sodium phenylbutyrate and taurursodiol, that are aimed at preventing nerve cells from dying. Klee and Amylyx co-CEO Josh Cohen began pursuing the drug when they were undergraduate students at Brown University. They won their first approval in June, when Canadian regulators granted the treatment, sold under the brand name Albrioza, conditional approval based on promising clinical evidence.
ALS is a progressive disease in which nerve cells that control movement, swallowing and breathing gradually die. About 30,000 people in the U.S. alone have the disease, which can be inherited or occur spontaneously. Patients generally die within two to five years after symptoms start, and better treatments are desperately needed. If approved, Amylyx’s medicine would become only the third major medicine authorized in the U.S. to slow the disease.
The regulatory process in the U.S. has been challenging. Amylyx shares plummeted 23% on Sept. 2 after the agency posted briefing documents that cast doubt on whether the new data would be sufficient to gain approval. The shares lost another 5.1% on Tuesday, when the market reopened after the Labor Day holiday. They were up 4.4% to $17.90 at the close Wednesday in New York.
Larger trial
Amylyx is expected to complete a larger trial in late 2023 or early 2024, the FDA said in briefing documents released Sept. 2. The timing puts the agency in “a challenging situation of potentially making a regulatory decision that may not be subsequently aligned with the results of the ongoing study,” FDA staff said in briefing documents.
While the FDA isn’t legally required to follow its advisory panels, it’s under public pressure not to ignore them without a good reason. Last year, three members of the panel now evaluating the Amylyx drug quit in protest when the agency approved Biogen Inc.’s Alzheimer’s drug Aduhelm, even though the group had roundly rejected it in late 2020.
Aduhelm was approved using a special accelerated mechanism that allows medicines to receive tentative clearance based on their ability to improve lab test results that are likely to predict clinical benefit. The problem in using accelerated approval for Amylyx is that there weren’t any such lab measures in its trials, the FDA said in its briefing documents.
Despite the FDA’s doubts about the new analysis, the agency’s comments on the desperate need for new ALS treatments and its regulatory flexibility suggest the agency is still looking for a way to approve Amylyx’s drug, SVB Securities analyst Marc Goodman wrote in a note to clients Friday.
Many ALS patient groups want the drug to be approved. How the FDA handles the Amylyx application could be a signal of how the agency intends to approach other rare neurodegenerative diseases.
It’s been “challenging” to see AMX0035 compared with Biogen’s Aduhelm, Amylyx’s Cohen said in the interview last month. Besides the fact they treat neurodegenerative diseases and were the subject of FDA meetings, there are no similarities between the drugs, he said.
Nonetheless, “it’s hard to imagine that’s not factoring into people’s choices and decision making, and I think that frankly puts us in a tough position,” Cohen said.
