Phenylbutyrate/Taurursodiol Submitted to FDA for Approval for Amyotrophic Lateral Sclerosis

A new drug application (NDA) was submitted to the Food and Drug Administration (FDA) for sodium phenylbutyrate (PB)/taurursodiol (TURSO) combination (AMX0035; Amylyx Pharmaceuticals, Cambridge, MA) for amyotrophic lateral sclerosis (ALS) treatment.  

The NDA submission to the FDA is based on data from the CENTAUR trial. In the randomized placebo-controlled trial, 137 participants were treated with PB/TURSO or placebo. Participants treated with PB/TURSO vs placebo had statistically significant slowing of disease progression as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). In the open-label extension study (NCT03488524), participants have been followed for over 3 years. Interim survival analysis at 3 years showed that those who had PB/TURSO during the blinded phase had a 44% lower risk of death. Median survival in those given PB/TURSO vs placebo in those first 6 months was 6.5 months longer than that seen in people who took placebo. Gastrointestinal adverse events occurred more frequently with PB/TURSO.
 
“This submission brings hope to people living with ALS and their families and caregivers,” said Merit Cudkowicz, MD, coprincipal investigator of the CENTAUR trial and cofounder of the Northeast ALS Consortium, director of the Healey & AMG Center for ALS and chair of Neurology at Massachusetts General Hospital and the Julieanne Dorn professor of Neurology at Harvard Medical School. “We are honored to have led the collaboration between the Healey & AMG Center for ALS, ALS Finding a Cure, the ALS Association, and NEALS that made the CENTAUR trial a reality, the efforts and results of which made this NDA submission possible.” 
 
“For people living with ALS and their physicians, this is a significant development offering hope of a potential new treatment option that has been shown to slow ALS disease progression and extend the time families that face this life-threatening disease have together,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR trial, investigator at the Healey & AMG Center for ALS at Massachusetts General Hospital and assistant professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. 
 
The possibility of an expanded access program (EAP) in the US for PB/TURSO is currently being explored.