CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) has accepted for review its New Drug Application (NDA) for AMX0035 (sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine)) for the treatment of amyotrophic lateral sclerosis (ALS). The FDA has granted Priority Review and assigned a Prescription Drug User Fee Act date for AMX0035 of June 29, 2022, the target date by which the FDA intends to complete its review and take action on the NDA. The Agency noted that it is currently planning to hold an advisory committee meeting to discuss the application. Amylyx additionally is preparing to submit an Expanded Access Program (EAP) to the FDA for launch in the United States in the coming months for patients who are ineligible for participation in the global Phase 3 PHOENIX clinical trial.

“We are excited about this milestone and are preparing our team to be able to launch commercially if the FDA review results in an approval,” said Justin Klee, Co-CEO, Director and Co-Founder of Amylyx. Joshua Cohen, Co-CEO, Chairman and Co-Founder of Amylyx added, “Our team is committed to bringing a potential new treatment, if approved, to people living with ALS as efficiently as possible, as each moment counts.”

“The acceptance of our NDA for review by the FDA brings us one step closer to bringing a potential new treatment to people living with ALS,” said Tammy Sarnelli, Global Head of Regulatory Affairs of Amylyx. “We thank everyone who participated in the CENTAUR trial, including the trial investigators, the ALS community, our partners and our team.”

The NDA submission to the FDA was based on data from the CENTAUR trial, a randomized, double-blind, placebo-controlled Phase 2 clinical trial conducted at 25 centers of the Northeast ALS Consortium (NEALS), evaluating 137 people with ALS. In this trial, participants receiving AMX0035 demonstrated statistically significant reduction in clinical 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 a survival analysis conducted in all randomized participants from the CENTAUR trial 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 demonstrated 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 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 Medicine¹ (NEJM) and Muscle and Nerve.²

“There is a lot of progress in ALS research; and now with AMX0035’s NDA acceptance, we believe we are one step closer to a potential new treatment option,” 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 look forward to seeing AMX0035 potentially progress through the regulatory review process as we continue to investigate its therapeutic potential in the global Phase 3 PHOENIX clinical trial as part of the collaboration with the Northeast ALS (NEALS) Consortium and the Treatment Research Initiative to Cure ALS (TRICALS) in Europe.”

“Those living with ALS are in urgent need of new therapies,” 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. “If approved, AMX0035 may provide people with ALS more shared memories and quality time with their loved ones.”

Marketing Application Reviews and Phase 3 Clinical Trial
Amylyx currently has marketing applications under review for AMX0035 in Canada and the United States. Amylyx plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in the first quarter of 2022.

Enrollment for the global Phase 3 PHOENIX clinical trial (NCT05021536) continues in the United States and Europe. The trial is designed to provide additional safety and efficacy data for AMX0035 for the treatment of ALS to further support our global regulatory efforts.

Amylyx looks forward to submitting its EAP for launch in the United States to run in parallel with the Phase 3 PHOENIX clinical trial and marketing application reviews. Details on the timing and eligibility criteria for participation in the planned EAP will be shared once available. When available, further information will be posted on the Amylyx website at www.amylyx.com.

About the CENTAUR Trial
CENTAUR was a multicenter Phase 2 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 reducing clinical decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

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

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.

About AMX0035
AMX0035 is a proprietary oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), which is a small molecular chaperone designed to reduce the UPR, preventing cell death resulting from the UPR, and taurursodiol (TURSO; also known as ursodoxicoltaurine)), which is a Bax inhibitor designed to reduce cell death through apoptosis. PB and TURSO were combined in a fixed-dose formulation in an effort 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 clinical-stage biopharmaceutical company working on developing a novel therapeutic for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter.

Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements.” Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the potential approval of AMX0035 in the United States for the treatment of ALS in the United States and other jurisdictions; the potential of AMX0035 as a treatment for ALS; Amylyx’ ability to successfully commercialize AMX0035 for the treatment of ALS, if approved; expectations related to Amylyx’ preclinical studies and clinical trials, including the design, timing and results of Amylyx’ Phase 3 PHOENIX trial; and expectations regarding our longer-term strategy. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities and planned IND-enabling studies, Amylyx’ ability to execute on its strategy, regulatory developments in the United States, Canada, the European Union and other jurisdictions, Amylyx’ ability to fund operations, and the impact that the current COVID-19 pandemic will have on Amylyx’ clinical trials and pre-clinical studies, supply chain, and operations, as well as those risks and uncertainties set forth in its registration statement on form S-1 filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

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¹  https://www.nejm.org/doi/full/10.1056/NEJMoa1916945
²  https://onlinelibrary.wiley.com/doi/10.1002/mus.27091