Yesterday was the long-awaited second meeting of the FDA’s independent expert panel to weigh in on Amylyx’s ALS drug, and, this time, AMX0035 came away with a victory. New information that Amylyx provided, which included new analyses of survival data from its main study and biomarker results from a phase 2 trial of the drug in Alzheimer’s disease, was able to sway some members to change their negative opinion from the last time they met.
After a meeting in March that resulted in a 6-4 vote against recommending AMX0035, yesterday, the peripheral and central nervous system drugs advisory committee voted 7-2 that the evidence of effectiveness was sufficient to support accelerated approval.
The two members who voted against efficacy made it clear that they would still prefer to wait for the results of the ongoing phase 3 trial, PHOENIX.
The FDA will make a decision on AMX0035's final approval by Sept. 29.
After the negative AdComm vote in March, the company submitted more analyses, and the agency took the unusual step of asking its expert panel to vote again based on the new evidence. Amylyx submitted new analyses of survival data from its main study, the phase 2 CENTAUR trial, along with biomarker results from a phase 2 of the drug in Alzheimer’s disease.
The AdComm's positive vote yesterday is a victory for advocacy groups, which have long backed the drug's approval given the unmet need, but the news did come as somewhat of a surprise. The FDA's briefing documents, released prior to the meeting, noted Amylyx’s new analyses were still not “sufficiently independent or persuasive” to serve as confirmatory evidence of AMX0035's effectiveness.
The documents described several issues including that Amylyx used old data to assess response rates and estimate survival benefit, while also noting that its survival predictions based on natural history data had “a variety of concerns.” As for the biomarker results from the Alzheimer’s study, the agency noted that the relevance to ALS is unknown.
Advocacy groups and individuals, nonetheless, pushed for an approval instead of waiting for the Phoenix data, noting thousands of patients that will not live to see the results of the trial. People with ALS have a short life expectancy and there is no cure. By the time of diagnosis, symptoms have started to take over. The panel was, of course, also asked to consider the unmet need of ALS; there are only two treatments approved for the degenerative disease. Neither show both slowing in functional decline and a survival benefit, which is Amylyx’s key contending points.
During the public comment period, speakers harped on how Canadian regulators approved the drug with much less evidence. Opposing speakers said better evidence is necessary, stating that since Canada’s standard is lower, the U.S. shouldn’t be influenced by the country’s decision.
One opposing speaker argued that the FDA told the company again and again what is needed for the drugs approval, only for the company to argue with the criticism. “We all wish the company had done a better job of gathering evidence,” the speaker said.
In June, Health Canada granted conditional approval to the med, AMX0035, under the brand name Albrioza.
One of the voting panel members was “struck” by patients’ participation in the public session, as well as the thousands of comments submitted by patients and families. Another agreed that it's important to pay attention to patients and patient’s clinicians in this matter. Another panel member said the evidence is “modest” at best.
A tiff broke out between the panel as one member asked about the pricing of the drug, as another attempted to shut the question down as it wasn’t a “scientific matter.” The point required an FDA member to shut down the disagreement, making it clear that cost is not a consideration in the agency’s assessments.