CAMBRIDGE, Mass.–(BUSINESS WIRE)–Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today announced the submission of safety and tolerability data for AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO; also known as ursodoxicoltaurine]) as assessed in the CENTAUR and PEGASUS clinical trials in participants with amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), respectively. The data support the overall safety profile of AMX0035, as the results of this analysis show that the incidence of adverse events was generally similar between the AMX0035 and placebo groups in both groups of trial participants.
“The results of this analysis provide additional information and clarification on the overall safety and tolerability of AMX0035 in people with two different conditions, ALS and AD, and how these diseases might impact on the results,” said Sabrina Paganoni, MD, Ph.D., principal investigator of the CENTAUR trial, investigator at the Healey & AMG Center for ALS at Massachusetts General Hospital, and associate professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital. “The comparison of TEAEs in the CENTAUR and PEGASUS clinical trials suggests that the overall higher incidence of TEAEs in CENTAUR trial participants, including muscle weakness and falls, may be attributed to the natural progression of ALS , as they have not been observed in people with Alzheimer’s disease.”
In the CENTAUR trial, participants (AMX0035, n=89; placebo, n=48) who completed the 24-week randomized phase were eligible to enroll in an open-label extension phase and receive AMX0035 (≤ 132 weeks , week 24 reported). PEGASUS was a 24-week randomized trial in adults with AD or mild cognitive impairment (AMX0035, n=51; placebo, n=44). Assessing the safety and tolerability of AMX0035 was the primary objective of both trials. The results of the summary of clinical trials showed that:
The majority of TEAEs associated with AMX0035 were gastrointestinal, consistent with the observed individual safety profiles of AMX0035 components.
In both trials, diarrhea and, to a lesser extent, abdominal discomfort/pain, abdominal distension and dyspepsia were more common with AMX0035 compared to placebo.
No new safety signal has been identified.
While the majority of participants in the Phase 2 studies experienced TEAEs, they were largely non-serious, mild or moderate in intensity, and rated as unrelated to study drug treatment.
The AD results shed further light on the safety profile of AMX0035, as the TEAEs in the CENTAUR trial appear to have been largely disease-related.
Further comparison of the TEAEs in the two trials suggests that the overall higher incidence of TEAEs in the CENTAUR trial was attributable to symptoms of the natural progression of ALS, namely muscle weakness and falls, which were among the The most common EIATs in CENTAUR.
“We are committed to discovering and developing new treatment options that may offer hope and expand function to people with neurodegenerative diseases affected by the progressive loss of certain abilities,” said Machelle Manuel, Ph. .D., Head of Global Medical Affairs for Amylyx. “We are pleased to share the results of this analysis further characterizing the safety profile of AMX0035 with the AAN medical and scientific community this year.”
The abstract, “Safety of a Fixed-Dose Coformulation of Sodium Phenylbutyrate and Taurursodiol in Amyotrophic Lateral Sclerosis and Alzheimer’s Disease: Integrated Clinical Trials Experience”, has been selected for oral presentation in the ALS and Motor Neuron Disorders scientific session, and will be presented Monday, April 4, 2022 (1:00-3:00 p.m. PT / 4:00-6:00 p.m. ET).
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 unfolded protein response (UPR), preventing cell death resulting from UPR, and taurursodiol (TURSO; also known as ursodoxicoltaurine), which is a Bax inhibitor designed to reduce cell death by apoptosis. PB and TURSO were combined in a fixed dose formulation with the aim of reducing neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondria-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.
About the CENTAUR Trial
CENTAUR was a phase 2 multicenter clinical trial in 137 participants with ALS, comprising a 6-month randomized placebo-controlled phase and a long-term open-label follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
Overall, the reported rates of adverse events and discontinuations were similar between the AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed CENTAUR data is published in the New England Journal of Medicine (NEJM) and Muscle and nerve.
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 the PEGASUS Trial
PEGASUS (NCT03533257) was a randomized, double-blind, multicenter, placebo-controlled trial evaluating the safety, tolerability, and activity of AMX0035 in 95 adults with dementia or late-onset mild cognitive impairment (MCI) due to MA over 24 weeks of treatment. The trial was designed to assess tolerability in this patient population while evaluating measures of efficacy and various disease-relevant markers to allow assessment and correlation of imaging-based markers, neurobiological changes , functional measures and cognitive outcomes in a large group of people. with AD.
About Amylyx Pharmaceuticals
Amylyx Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company working to develop a novel treatment for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. For more information, visit www.amylyx.com and follow us on LinkedIn and Twitter. For investors, please visit www.investors.amylyx.com.
Statements in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because these statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by these forward-looking statements. These statements include, but are not limited to, statements regarding: Amylyx’s strategy, business plans and objectives for 2022 and beyond; the potential of AMX0035 as a treatment for ALS and AD and the efficacy and safety profile of AMX0035; the timing, progress and results of our PHOENIX Phase 3 clinical trial of AMX0035; the potential of AMX0035 or other future therapeutic candidates as a treatment for neurodegenerative diseases; and expectations regarding our longer-term strategy. All forward-looking statements contained in this statement are based on management’s current expectations regarding future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those stated. or implied by these forward-looking statements. . Risks that contribute to the uncertain nature of forward-looking statements include: the success, cost and timing of Amylyx’s program development activities, Amylyx’s ability to execute its business and regulatory strategy, regulatory developments, expectations regarding the FDA’s timeline to review AMX0035 for the treatment of ALS, Amylyx’s ability to fund its operations and the impact the ongoing COVID-19 pandemic will have on Amylyx’s operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’s Annual Report on Form 10-K for the fiscal year ended December 31, 2021, and subsequent filings with the SEC. 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 these statements to reflect events that occur or circumstances that exist after the date on which they were made.