Post Hoc Analysis Suggests Combination Sodium Phenylbutyrate/Taurursodiol Prolongs Survival in Amyotrophic Lateral Sclerosis

A post hoc analysis of data from the CENTAUR trial (NCT03488524) estimates that combined sodium phenylbutyrate (PB)/taurursodiol (TURSO) (AMX0035; Amylyx Pharmaceuticals, Cambridge, MA) resulted in a longer median survival duration for participants with amyotrophic lateral sclerosis (ALS) than suggested by the prespecified intention-to-treat (ITT) analysis. 

Initial prespecified ITT analysis showed a median survival duration of 6.9 months longer in those treated with PB-TURSO vs placebo in the 6-month double-blind period (hazard ratio [HR], .57; 95% CI, .35–.92; P=.023). Long-term, after approximately 3 years of treatment, those treated with PB-TURSO vs placebo in the double-blind period had a 4.8-month longer median survival (HR .64; 95% CI, .42-1.00; P=.048).

The new post hoc analysis is a rank-preserving structural failure time model (RPSFTM) commonly used in oncology trials or for other diseases with short life expectancy. This analysis adjusts for the number of participants treated with placebo who did not survive into the open-label study. Using this analysis, those treated with PB-TURSO vs placebo in the double-blind period had a 10.6-month longer median survival.

“The results of these long-term analyses of the CENTAUR trial provide further evidence that PB-TURSO may offer a survival benefit in people with ALS and provide insights into potential new approaches to analyze survival data in ALS trials,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General and associate professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. “As a serious and fatal disease, time is invaluable for those living with ALS and their families, and any potential treatment that may offer more time is important.”

Adverse events with PB-TURSO included diarrhea, abdominal discomfort/pain, abdominal distension, and dyspepsia. 

A new drug application has been submitted to the Food and Drug Administration (FDA) with a decision expected at the end of June 2022. PB-TURSO continues to be studied in ALS with the phase 3 PHOENIX trial (NCT05021536) designed to generate additional safety and efficacy data for PB-TURSO for the treatment of ALS.