Combination ALS therapeutic nonsuperior to placebo in phase 3 clinical trial

Key takeaways:

• The therapy was hypothesized to simultaneously mitigate mitochondrial dysfunction.
• The PHOENIX trial included 664 individuals with ALS given combination therapy or placebo for 48 weeks.

DENVER — A combination therapeutic for amyotrophic lateral sclerosis was nonsuperior to placebo over 48 weeks in a phase 3 clinical trial, according to a presenter at the American Academy of Neurology annual meeting.

“The treatment is a fixed combination of two small molecules,” Leonard H. Van den Berg, MD, PhD, a professor of neurology at UMC Utrecht Brain Center and director of the Netherlands ALS Center, said during his presentation. “(The treatment) is hypothesized to simultaneously mitigate mitochondrial dysfunction, leading to neuronal degeneration in [ALS].”

Van den Berg and colleagues sought to examine the combination therapeutic of sodium phenylbutyrate and taurursodiol (Relyvrio, Amylyx Pharmaceuticals) in the phase 3 PHOENIX study.

Their randomized clinical trial included 664 individuals with either clinically definite or clinically probable ALS, fewer than 24 months from symptom onset and who were previously prescribed a stable dose of either riluzole or edavarone. Participants were randomized on a 3:2 basis to receive either Relyvrio (n = 397; mean age 60 years; 63% male) or placebo (n = 267; mean age 58.8 years; 60% male) for 48 weeks, with the option to enter an open-label extension lasting through 108 weeks.

The primary endpoint was change from baseline to week 48 in the ALS Functional Rating Score-R (ALSFRS-R) total score, with secondary endpoints of change from baseline to week 48 in the ALS Assessment Questionnaire (ALSAQ-40) total score as well as overall survival.

A total of 57% of all participants completed the 48-week follow-up.

The researchers reported that change in ALSFRS-R score for those in the treatment group was -14.98 and -15.32 for the placebo group by week 48, while mean change in ALSAQ-40 was 39.8 for the treatment group and 38.4 for those given placebo. Overall survival data is still outstanding; however, the treatment was generally well tolerated, Van den Berg and colleagues wrote.

“Amylyx announced it has started the process to remove [Relyvrio] from markets in the U.S. and Canada based on the results I shared today,” Van den Berg said. “Despite promising results in the phase 2 study, there were no difference between groups in the phase 3 study.”