Title: Relyvrio’s Ineffectiveness in Large ALS Clinical Trial: What Does This Mean for Amylyx Pharmaceuticals and Patients?
Amylyx Pharmaceuticals announced on February 24, 2023, that the results from a large phase 3 clinical trial called Phoenix did not demonstrate a significant benefit of their drug for amyotrophic lateral sclerosis (ALS), named Relyvrio. According to Amylyx, the drug did not outperform a placebo in improving participants’ ALS functional scale – which measures their ability to breathe, swallow, and speak after 48 weeks – nor did it significantly enhance patient-reported quality of life, overall survival, or respiratory function.
Co-CEOs of Amylyx, Justin Klee and Joshua Cohen, expressed their disappointment and surprise with the Phoenix results in a news release: “We are deeply disappointed by the PHOENIX results. Our team will continue to engage with regulatory authorities and the ALS community over the next eight weeks to discuss these findings.” They emphasized that their decisions would be guided by two principles: “doing what is right for people living with ALS and being informed by regulatory authorities and the ALS community, as well as what the science tells us.”
The discussions within the next eight weeks may include the withdrawal of Relyvrio from the market. Amylyx has stated that the drug and patient support services will remain available for people living with ALS, but they have paused promotion of Relyvrio.
The nonprofit ALS Association acknowledged the trial’s outcome and expressed their sympathy for the ALS community, stating, “We are saddened by today’s news and our hearts go out to everyone in the ALS community. We are grateful to the FDA and Amylyx for working closely with the ALS community throughout this process.”
ALS, also known as Lou Gehrig’s disease, is a fatal neurodegenerative condition that affects approximately 30,000 individuals in the United States. It targets the nerves responsible for muscle movement, progressively impairing abilities to move, speak, swallow, and eventually breathe. The average time from symptom development to death is typically two to five years.
In September 2022, Relyvrio received approval from the US Food and Drug Administration (FDA) based on a small phase 2 trial that showed a modest slowing of disease progression. However, the FDA’s decision was controversial because proof of the drug’s efficacy did not meet typical standards at that time.
Holly Fernandez Lynch, assistant professor of medical ethics and law at the University of Pennsylvania, explained the situation: “ALS is a terrible disease. There are no good treatment options. There is an insatiable desire to develop something that is going to modify the course of this disease.” Relyvrio’s approval was contingent on extensive lobbying from ALS patient advocacy groups and a promise from Amylyx to withdraw the drug if the larger phase 3 trial failed to confirm benefits.
Now that the Phoenix results show Relyvrio’s ineffectiveness, it is up to Amylyx Pharmaceuticals to withdraw the drug from the market. If the company decides against doing so, the FDA retains the power to pull it from the shelves, although this would be a much more lengthy process.
Fernandez Lynch acknowledges that the gamble made by the FDA in this case was reasonable but raises concerns regarding how much revenue Amylyx generated from selling an ineffective drug. Relyvrio costs around $158,000 per year and brought in $381 million in sales and $49 million in profits for Amylyx in 2023.
She stated, “I think this is an example where, if you’re going to allow drugs on the market with uncertainty, then we need to have greater control over the pricing.”
These developments in the ALS treatment landscape underscore the challenges associated with developing effective treatments for this devastating disease. The future of Relyvrio and Amylyx Pharmaceuticals hangs in the balance as the company grapples with these complex ethical, regulatory, and financial issues.
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