In the phase 2 CENTAUR study (NCT03127514). Participants with amyotrophic lateral sclerosis (ALS) treated with a coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) (AMX0035; Amylyx Pharmaceuticals, Cambridge, MA) resulted in slowing of functional decline and extends survival for up to 6 months. PB-TURSO was designed to improve survival by mitigating both endoplasmic reticulum (ER) stress and mitochondrial dysfunction.
Participants age 18 to 80 with a definitive diagnosis of ALS within the prior 18 months using the revised El Escorial criteria were eligible to enroll. The El Escorial criteria include: clinical evidence of both upper and lower motor neuron signs in 3 or more body regions and symptom onset. Median overall survival was 25 months among participants originally randomly assigned to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% CI, 0.34–0.92; P=0.023).
“These results support that AMX0035 has both functional and long-term survival benefits,” commented Dr. Merit Cudkowicz, director of the Healey and AMG Center for ALS, chief of Neurology at Mass General, chief medical officer of ALS Finding a Cure, and the Julieanne Dorn professor of Neurology at Harvard Medical School. “ALS is a serious disease that progresses rapidly. With these results, we have shown that AMX0035 may provide patients hope and the chance to function better and live longer lives. On behalf of ALS Finding a Cure, our colleagues, and foundations that supported us, I want to thank all participants not only in this study, but also in all previous ALS studies, for their critical role in helping to reach wonderful milestones like this.”
In CENTAUR, 137 adult participants with ALS were randomly assigned 2:1, to receive orally administered fixed-dose of PB-TURSO (n=89) or placebo (n=48). Participants completing the 24-week randomized phase were eligible to receive PB-TURSO in the open-label extension (OLE). An all-cause mortality analysis incorporated all randomized participants. After the 24-week treatment vs placebo phase, 92% of participants continued receiving or switched to PB-TURSO on an open-label basis. However, participants and site investigators were blinded to the initial 24-week treatment assignment throughout the study.
The study measured the effect of slowing decline in Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) total score in participants treated with PB-TURSO vs placebo over 6 months (24 weeks). Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR.
Magdalena Szaflarski, PhD
Alyssa R. Rosen, MD
James Geyer, MD, and Thomas Patton, MD