ADVERTISEMENT
New ALS Drug Gets OK From FDA, Despite Lingering Efficacy Concerns
On Thursday, the US Food and Drug Administration (FDA) approved sodium phenylbutyrate/taurursodiol (Relyvrio) to treat patients living with amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig’s disease.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” stressed Billy Dunn, MD, director of the Office of Neuroscience, Center for Drug Evaluation and Research, FDA, in a news release announcing the approval.
The authorization came through amid criticism that the FDA prioritized patient appeals and other outside voices instead of waiting for robust, Phase 3 trial evidence to cement proof of the drug’s efficacy.
Relyvrio is only the latest neurological drug approval to garner scrutiny toward the regulatory agency. Currently, the FDA is grappling with 2 separate governmental inquiries into last year’s approval of Aduhelm to slow Alzheimer disease, despite lack of evidence that the drug succeeds in achieving this goal.
News: FDA Rolls Out 5-Year Plan for Addressing Rare Neurodegenerative Diseases
Sodium phenylbutyrate/taurursodiol, produced by Amylyx Pharmaceuticals, is a power-based drug that combines two older ingredients used to treat other conditions. One (sodium phenylbutyrate) is a prescription medication for liver disorders while the other (taurursodiol) is a dietary supplement that is most known for its use in Chinese medicine. It can be administered orally by dissolving in room temperature water or through a feeding tube.
The question of the drug’s efficacy and, by extension, the FDA’s decision to approve it centers around the fact Relyvrio has, so far, only been studied up through a Phase 2 clinical trial against placebo. The FDA granted the drug’s application both Priority Review designation and orphan drug designation, which “provides incentives to assist and encourage the development of drugs for rare diseases.”
CENTAUR, a multicenter, randomized, double-blind trial included 137 patients with ALS. Over a 6-month period, 89 participants were randomly assigned to receive sodium phenylbutyrate/taurursodiol while the remaining 48 received placebo. Researchers continued to evaluate participants over an open-label extension long-term follow up phase.
The results of the study, published in the New England Journal of Medicine, Muscle & Nerve, and the Journal of Neurology, Neurosurgery, and Psychiatry, showed that in a modified intention-to-treat analysis, the mean rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) was -1.24 points per month with the active drug and -1.66 points per month with placebo (P=0.03).
Quiz: Researchers recently advised that what be added to ALS assessments?
“Sodium phenylbutyrate–taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks,” researchers concluded. They continued to note that, “Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate–taurursodiol in persons with ALS.” The CENTAUR trial was funded by Amylyx, as well as the ALS ACT grant and the ALS Ice Bucket Challenge.
The Phase 3 trial of Relyvrio is currently underway, with results from the 600-patient study expected in 2024. Amylyx has indicated that should the Phase 3 results fail to confirm the drug’s efficacy, the company would pull its drug from the market. Many have noted, though, that neither the FDA nor Amylyx specified what would constitute successful versus failing trial results.
In a summary memorandum explaining its approval, the FDA noted that "There are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness that exceeds that which might typically remain following a conclusion that substantial evidence of effectiveness has been demonstrated," but "given the serious and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this instance."
References
