An Amylyx Pharmaceuticals amyotrophic lateral sclerosis drug that won a controversial FDA approval based on mid-stage clinical trial results has failed to meet all of the goals of a larger Phase 3 clinical trial, putting the future of the drug and the company in question.
According to preliminary results announced Friday, the drug, Relyvrio, was not better than a placebo at slowing progression of the neuromuscular disorder. The study’s primary endpoint was to show a change in score according to a rating scale used to assess function in ALS patients. Cambridge, Massachusetts-based Amylyx said this result was not statistically significant. The drug also did not achieve statistical significance on secondary goals that include measures of breathing function and quality of life.
Detailed results were not disclosed, but the company said data from the clinical trial will be presented at an upcoming medical meeting and published in a medical journal later this year. In the near term, the company has set an eight-week timeline to determine its next steps for Relyvrio. Those steps could include voluntarily withdrawing the drug from the market, co-CEO Justin Klee said, speaking during a Friday conference call. To inform this decision, Klee said the company will share the topline data with the FDA and Health Canada as well as the ALS community.
“As we consider our plans, we will be led by two key principles: doing what is right for people living with ALS informed by regulatory authorities and the ALS community, and doing what the science tells us,” Klee said.
Shares of Amylyx opened Friday at $2.99 apiece, down more than 82% from Thursday’s closing price.
Relyvrio is a fixed-dose combination of two compounds, each targeting a different neurodegenerative disease pathway. Hitting both pathways is intended to reduce cellular stress that contributes to neuronal cell death. The drug achieved positive results in a 137-patient placebo-controlled Phase 2 study that was the basis for its 2022 approval. The FDA had initially asked Amylyx to conduct a larger Phase 3 study to support a regulatory submission. But in explaining its decision to approve Relyvrio based on a single Phase 2 trial, the FDA said it was exercising “regulatory flexibility” due to the life-threatening nature of the disease, which has few treatment options.
Relyvrio’s approval was a traditional approval, not an accelerated one. Accelerated approvals require a post-marketing confirmatory clinical trial. But Amylyx remained committed to completing the Phase 3 study, expecting the additional data would be needed in other markets (ahead of the FDA decision, the Amylyx drug was approved in Canada, where it is marketed as Albrioza; European authorities last year issued a negative opinion on drug’s application). During the advisory committee preceding the FDA decision, Klee said Amylyx would withdraw Relyvrio from the market if it failed the larger clinical trial.
The Phase 3 study had a design similar to the Phase 2 study and it used the same clinical trial goals. But with four times as many patients evaluated for twice as long, this study was better-powered to detect the drug’s effects. In addition to the measures of function, the study had the additional goal of measuring overall survival. Co-CEO Joshua Cohen said survival data are not yet mature. While detailed results for the primary and secondary endpoints remain undisclosed, Klee said they speak to the heterogeneity of ALS—a single disease can be driven by multiple causes. The results also speak to the challenges of neurodegenerative disorders broadly, he added.
Amylyx has been evaluating whether Relyvrio’s approach to protecting neurons can also treat other neurodegenerative diseases. A Phase 3 test is ongoing in progressive supranuclear palsy; preliminary data are expected in 2025 or 2026. A Phase 2 study in Wolfram syndrome is expected to yield preliminary data in the second quarter of this year. The Amylyx pipeline also includes AMX0114, an antisense oligonucleotide targeting a gene that encodes an enzyme associated with neurodegeneration. Cohen said the company hopes to advance this program to the clinic in the second half of this year.
In 2023, Relyvrio/Albrioza accounted for $380.7 million in revenue, according to Amylyx’s annual report. While the company evaluates its next steps. the product will continue to be available to patients in the U.S. and Canada, Klee said. Amylyx will no longer promote the drug, but the company’s patient support services will remain in place. Amylyx completed 2023 with $371 million in cash. Chief Financial Officer Jim Frates said Amylyx has the financial resources to focus on its earlier-stage programs, but that work may be under a different company structure. He declined to elaborate, saying “now is not right time to give clear plans.”
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