Even with new data, FDA reviewers remain skeptical about AMX0035, the investigational drug for amyotrophic lateral sclerosis (ALS) getting a rare second chance before an FDA advisory committee on Wednesday.
Post hoc analyses from drugmaker Amylyx Pharmaceuticals do not appear to provide "independent confirmatory evidence" of the clinical effect of AMX0035 in ALS, FDA reviewers wrote in a .
Wednesday's meeting marks the second time the drug will go before the agency's Peripheral and Central Nervous System Drugs Advisory Committee.
In March, the advisory committee voted that the findings of a single trial for AMX0035, a proprietary combination of sodium phenylbutyrate and taurursodiol, did not support a conclusion that the drug was effective in ALS.
The 6-4 vote was based on findings from the phase II CENTAUR trial and was in line with the FDA's position at the time that CENTAUR results were not "sufficiently persuasive."
After the meeting, Amylyx submitted additional analyses of survival data from CENTAUR and its open-label extension, along with biomarker evidence from the phase II study of AMX0035 in Alzheimer's disease.
The new information was intended to be confirmatory evidence to accompany the primary result of the CENTAUR study. But it "contained no new data from the CENTAUR study or its open-label extension; the submission consisted of new analyses of previously submitted survival data," FDA reviewers wrote.
"The submitted biomarker data are not clear evidence of a CNS [central nervous system] effect or a potential clinical benefit in patients with ALS," they added.
In certain circumstances, the FDA can conclude that one adequate and well-controlled clinical investigation plus confirmatory evidence is sufficient to establish effectiveness for a new drug.
That's the crux of the question FDA advisory committee members will vote on Wednesday: whether the available evidence for AMX0035 -- both the new information presented and the data reviewed at the March meeting -- is sufficient to support the drug's approval in ALS.
The committee's vote can involve more than just trial data, the agency noted. "In addition to the prior and new evidence presented, you may take into account in your vote the unmet need in ALS, the status of the ongoing phase III trial, and the seriousness of ALS," the FDA wrote in its instructions to advisory committee members.
The ALS community has urged the FDA to be more flexible about new drugs given the devastating effect of the disease. Lawmakers also have pressed the FDA to get new ALS therapies to patients.
In June, to approve AMX0035 (marketed as Albrioza) for ALS, contingent on the provision of data from the drug's ongoing phase III trial of about 600 ALS patients. Topline results from the trial are expected in 2024.
"We believe AMX0035 is an important potential new treatment in the fight against ALS, and we are working against the ALS clock and the ALS community does not have time to wait," Amylyx said in a statement issued last Friday. "We remain steadfast in our commitment to bringing AMX0035 to people living with ALS and their families around the world."