CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. today announced it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for AMX0035 (sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine)) for the treatment of amyotrophic lateral sclerosis (ALS).

“We are excited to share with the ALS community the exciting milestone that we have submitted our NDA to the FDA for review,” said Justin Klee, Co-CEO, Director and Co-Founder of Amylyx. Joshua Cohen, Co-CEO, Chairman and Co-Founder of Amylyx added, “Our team has worked and continues to work around the clock as we know time is of the essence for people living with ALS and their families. We will continue to keep the community closely updated on our progress.”

“We will continue to work closely with the FDA throughout the review process to move AMX0035 toward a potential regulatory approval as quickly and efficiently as possible,” said Tammy Sarnelli, Global Head of Regulatory Affairs of Amylyx. “We are so inspired by the people who participated in CENTAUR, the trial investigators, the ALS community and our partners and team, and we will continue to work tirelessly on behalf of you all.”

The NDA submission to the FDA is based on data from the CENTAUR trial, a placebo-controlled study evaluating 137 people with ALS. In this study, participants receiving AMX0035 had statistically significant slowing of functional decline at the end of the 6-month randomized phase as measured by the Revised ALS Functional Rating Scale (ALSFRS-R), the most commonly used scale in clinics worldwide to measure function in ALS. In an interim survival analysis conducted in all randomized participants from CENTAUR who were followed for up to three years, which included participants who continued to receive AMX0035 in an open-label extension phase during the follow-up period, participants who started on AMX0035 during the placebo-controlled phase of CENTAUR showed a 44% lower risk of death compared to those who started on placebo during the placebo-controlled phase (HR 0.56; 95% CI, 0.34-0.92). Median survival duration through the open-label long-term follow-up phase was 25.0 months (95% CI, 19.0-33.6 months) in the group that started on AMX0035 and 18.5 months (95% CI, 13.5-23.2 months) in the group that started on placebo, a 6.5-month difference. Overall, reported rates of adverse events and discontinuations were substantially similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle and Nerve.

“This submission brings hope to people living with ALS and their families and caregivers,” said Merit Cudkowicz, M.D., co-principal investigator of the CENTAUR trial and co-founder of the Northeast ALS Consortium, Director of the Healey & AMG Center for ALS and Chair of Neurology at Massachusetts General Hospital and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “We are honored to have led the collaboration between the Healey & AMG Center for ALS, ALS Finding a Cure, the ALS Association, and NEALS that made the CENTAUR trial a reality, the efforts and results of which made this NDA submission possible.”

“For people living with ALS and their physicians, this is a significant development offering hope of a potential new treatment option that has been shown to slow ALS disease progression and extend the time families that face this life-threatening disease have together,” said Sabrina Paganoni, M.D., Ph.D., principal investigator of the CENTAUR trial, investigator at the Healey & AMG Center for ALS at Massachusetts General Hospital and Assistant Professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital.

As previously reported, Amylyx filed a New Drug Submission (NDS) for AMX0035 for the treatment of ALS with Health Canada in June 2021. Amylyx also intends to submit a Marketing Authorization Application (MAA) for AMX0035 to the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) by approximately the end of 2021 and to initiate a global Phase 3 clinical trial with sites in Europe and the United States in the fourth quarter of 2021. The Phase 3 PHOENIX trial of AMX0035 for the treatment of people with ALS will assess the safety and efficacy of AMX0035 in an international population of approximately 600 participants and build upon findings from the CENTAUR trial. Amylyx is currently exploring the possibility of an Expanded Access Program (EAP) in the United States. If implemented, the EAP would run in parallel with the ongoing Phase 3 PHOENIX trial and marketing application reviews. Further information about the EAP is expected in the fourth quarter of 2021.

About the CENTAUR Trial

CENTAUR was a multicenter clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of slowing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

Overall, reported rates of adverse events and discontinuations were substantially similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group.

In an interim survival analysis conducted in all randomized participants from CENTAUR who were followed for up to three years, which included participants who continued to receive AMX0035 in an open-label extension phase during the follow-up period, participants who started on AMX0035 during the placebo-controlled phase of CENTAUR showed a 44% lower risk of death compared to those who started on placebo during the placebo-controlled phase (HR 0.56; 95% Confidence Interval (CI), 0.34-0.92). Median survival duration through the open-label long-term follow-up phase was 25.0 months (95% CI, 19.0-33.6 months) in the group that started on AMX0035 and 18.5 months (95% CI, 13.5-23.2 months) in the group that started on placebo, a 6.5-month difference.

The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General.

More information on the CENTAUR trial can be found at https://www.amylyx.com/pipeline/ or www.clinicaltrials.gov, NCT03127514 or NCT03488524.

About AMX0035

AMX0035 is an investigational product comprised of two complementary active agents, sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine), which were combined in a co-formulation to reduce neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

About Amylyx Pharmaceuticals

Amylyx Pharmaceuticals, Inc. is a pharmaceutical company working on developing a novel therapeutic for amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter.