Amylyx Pharmaceuticals is considering withdrawing its amyotrophic lateral sclerosis (ALS) drug, Relyvrio, from the market after disappointing results from the Phase 3 PHOENIX trial. The trial failed to show a significant benefit over placebo in key measures of disease progression.
The PHOENIX trial assessed Relyvrio's efficacy in improving the ALS Functional Rating Scale-Revised (ALSFRS-R), a measure of patients' ability to breathe, swallow, and speak. After 48 weeks, the drug did not outperform the placebo. Secondary endpoints, including patient-reported quality of life, overall survival, and respiratory function, also showed no significant improvement.
Company Response and Next Steps
"We are surprised and deeply disappointed by the PHOENIX results," stated Justin Klee and Joshua Cohen, co-CEOs of Amylyx, in a press release. The company plans to engage with regulatory authorities and the ALS community over the next eight weeks to discuss the trial's implications. A potential market withdrawal of Relyvrio is among the options being considered.
Currently, Relyvrio and its patient support services remain available, but Amylyx has paused promotional activities for the drug. The ALS Association expressed sadness at the news, emphasizing the urgent need for effective ALS treatments.
Background and Approval Controversy
ALS, also known as Lou Gehrig's disease, affects approximately 30,000 people in the United States. It is a progressive neurodegenerative disease that leads to paralysis, respiratory failure, and death, typically within two to five years of symptom onset.
Relyvrio received FDA approval in September 2022 based on data from a smaller Phase 2 trial that suggested a modest slowing of disease progression. However, the approval was met with controversy due to concerns about the strength of the evidence. Dr. Kenneth Fischbeck, a member of the FDA's advisory committee, noted that the single trial did not provide "substantial evidence with persuasiveness and robustness" to support its effectiveness.
Despite these concerns, the FDA granted approval after extensive lobbying from ALS patient advocacy groups and a commitment from Amylyx to consider withdrawing the drug if the Phase 3 trial failed to confirm its benefits. The ALS Association acknowledged the community's willingness to accept the risk of ineffectiveness in exchange for potential access to a life-extending treatment.
Financial Implications
Relyvrio is priced at approximately $158,000 per year. In 2023, it generated $381 million in sales and $49 million in profits for Amylyx. Holly Fernandez Lynch, a professor of medical ethics and law at the University of Pennsylvania, raised concerns about the financial gains made from a drug with uncertain efficacy, suggesting the need for greater pricing control when drugs are approved with limited evidence.
