The final amyotrophic lateral sclerosis (ALS) patient treated with oral AMX0035 in the CENTAUR study has completed all scheduled follow-up visits and researchers will now evaluate data collected on the potential treatment’s safety and efficacy, Amylyx Pharmaceuticals, its developer, announced.
“This trial has been an important partnership between industry and academia, and we look forward to analyzing the results gathered in this study,” Sabrina Paganoni, MD, PhD, principal investigator of the study at the Healey Center for ALS at Mass General and an assistant professor at Harvard Medical School and Spaulding Rehabilitation Hospital, said in a press release.
“Thank you to the participants and site study teams who have made this work possible,” Paganoni added.
AMX0035 is an orally available candidate therapy designed to minimize mechanisms linked to the death of nerve cells. It consists of two small molecules — tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate (PB) — that target signals within a cell’s mitochondria and endoplasmic reticulum, two compartments strongly implicated in cellular stress and nerve cell death.
Both TUDCA and PB were shown to effectively prevent cell death and damaging neuroinflammation in preclinical models of ALS.
The trial’s primary goal is to assess the tolerability and safety profile of AMX0035, with secondary goals looking for evidence of an ability to delay ALS progression. CENTAUR enrolled 132 people with a diagnosis of either sporadic or familial ALS, who were randomly assigned to twice-daily doses of AMX0035 or a placebo for 24 weeks.
Treatment effectiveness will be determined by changes in the ALSFRS-R scale, a doctor-reported instrument for monitoring disability progression in ALS.
Other post-treatment, 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.
People who completed the trial have the option of rolling into an open-label extension study, called CENTAUR-OLE (NCT03488524), in which they will either continue being treated with AMX0035 or — for those who were in the initial trial’s placebo group — begin using it. Enrollment began in this extension study in April 2018.
AMX0035 was given orphan drug status by the U.S. Food and Drug Administration in 2017 as a potential treatment for ALS.
CENTAUR was awarded an ALS Accelerated Therapeutics grant (ALS-ACT is an academic-foundation-industry partnership with ALS Finding a Cure, in collaboration with The Leandro P. Rizzuto Foundation), and financial support from the ALS Association, Northeast ALS Consortium, and Massachusetts General Hospital Neurology Clinical Research Institute.
“We’re thankful to everyone involved, and we are working hard to bring topline results to the community as quickly as possible,” said Patrick Yeramian, MD, chief medical officer of Amylyx.