AMX0035 Significantly Slows Disease Progression in ALS, Phase 2 Study Shows

Updated results from the CENTAUR Phase 2 trial show that Amylyx‘s investigational oral treatment, AMX0035, significantly slowed progression in treated amyotrophic lateral sclerosis (ALS) patients with rapidly advancing disease compared to those given a placebo.

The trial reached its primary goal shortly after its final patient examination in September.

Data show those given AMX0035 declined in existing abilities — as measured by ALS Functional Rating Scale-Revised (ALSFRS-R) scores that cover speech, swallowing, dressing and hygiene, among other daily functions — much more slowly than the placebo group over the trial’s 24 weeks.

Detailed results will be shared at a future medical meeting and published in a peer-reviewed scientific journal in the coming months, Amylyx said.

“Today marks a significant step forward in the fight to develop new treatments for ALS,” Sabrina Paganoni, MD, PhD, an assistant professor of physical medicine and rehabilitation at Harvard who is leading the CENTAUR study, said in a press release. “The study results highlight AMX0035 as a potentially beneficial new treatment for people with ALS.”

AMX0035 is a combination therapy that includes two small molecules — tauroursodeoxycholic acid and sodium phenylbutyrate — both of which act to prevent nerve cell death by blocking stress signals within the mitochondria (which provide cells with energy), and the endoplasmic reticulum (which is involved in making proteins).

Unlike other treatments in development, AMX0035 does not target the root cause of ALS. Instead, it aims to preserve the motor neurons that are progressively lost in ALS patients, causing clinical decline.

Evidence of lesser nerve cell death and inflammation was seen in preclinical models of ALS. These findings led to the opening of the  CENTAUR trial (NCT03127514), comparing the safety and efficacy of AMX0035 to a placebo in 132 ALS patients.

All enrolled were diagnosed with sporadic or familial ALS within the previous eight months, and all had rapidly progressing disease, a stringent enrollment criteria meant to provide the most powerful results possible, trial researchers said in a webinar.

Participants were randomized 2:1 to either AMX0035 or placebo twice-daily for 24 weeks (about six months), after which they were given the option to enter an open-label extension study and switch to or continue with this treatment. Almost all in CENTAUR — 90% of its patients — opted to do so, the company reported.

The trial’s primary goals also included measures of safety and tolerability; details were not released.

Secondary efficacy measures being evaluated include AMX0035’s impact on muscle strength, respiratory function, and biomarkers of ALS,  including markers of neuronal death and neuroinflammation.

“We are honored and humbled to have reached this milestone after working nearly seven years on the development of AMX0035,” said Joshua Cohen, CEO, chairman, and co-founder of Amylyx. “Thank you to each and every participant, family, physician, nurse, coordinator, vendor, and advisor who has and continues to work with us to better the lives of people with ALS.”

The study is a collaboration between Amylyx, ALS Finding a Cure Foundation and its Leandro P. Rizzuto Foundation, the ALS Association, Northeast ALS Consortium, and Massachusetts General Hospital Neurology Clinical Research Institute.

“ALS Finding a Cure is proud to have catalyzed and supported the CENTAUR study, and I am encouraged by what the results mean for people living with ALS. Our team at the Mass General Neurological Clinical Research Institute is proud of this collaboration with Amylyx and our colleagues in the Northeast ALS Consortium on this important study,” said Merit Cudkowicz, chief medical officer from ALS Finding a Cure.

“We are proud to have supported AMX0035 and Amylyx from an early stage and are very excited about what AMX0035 may accomplish for people with ALS,” said Neil Thakur, executive vice president for mission strategy at The ALS Association. “We are excited to continue to collaborate on this therapy in the future.”