CAMBRIDGE, Mass.–(BUSINESS WIRE)–May 5, 2022–
Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today announced the publication of long-term survival analyzes from the Phase 2 CENTAUR trial adjusted for treatment crossover of the placebo group. Post hoc analyzes suggested a greater survival benefit for AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO; also known as ursodoxicoltaurine]) when adjusting for a placebo crossover ranging from 10.6 to 18.8 months compared to 6.9 months observed in the original pre-specified intention-to-treat (ITT) analysis in participants with amyotrophic lateral sclerosis (ALS). These results are published in the peer-reviewed medical journal, Muscles and nerves.
“Trials that incorporate a crossover between placebo and active treatment are critically important in rapidly fatal diseases like ALS, however, this design may underestimate the clinical effect of experimental therapies,” said Machelle Manuel. , Ph.D., Head of Global Medical Affairs for Amylyx. “Fortunately, statistical models, like the RPSFTM, allow us to adjust the results for treatment crossover. Here, as with the pre-specified ITT analysis, we observed a significant survival benefit for AMX0035 in survival analyzes adjusting the treatment crossover, potentially offering people living with ALS and their families hope to share more memories and steps together.
The survival analyzes incorporated updated information on participants’ vital status from the previous interim ITT analysis. The final dataset compared time to death (all-cause mortality) from the time of randomization in the Phase 2 CENTAUR trial to the cutoff date of July 20, 2020 (longest follow-up, 35 months after randomization) and the date of the last visit of the participants in the open-label extension (OLE) phase (March 1, 2021, up to 42 months after randomization). Vital status could be determined for all participants except one who was censored at the last follow-up date. Post hoc analyzes performed included an RPSFTM analysis and a subgroup analysis.
- As of the July 2020 cutoff, the results of the final ITT overall survival analysis showed a significantly longer median survival time of 6.9 months in those initially randomized to receive AMX0035 compared to those initially randomized to receive a placebo (relative risk [HR], 0.57; 95% CI, 0.35 to 0.92; P =.023).
- As of the March 2021 cutoff, results showed a significantly lower risk of death and a longer median survival time of 4.8 months in people initially randomized to AMX0035 compared to those initially randomized to placebo (HR 0.64, 95% CI, 0.42-1.00; P =.048).
- The results of the statistical methods that take into account the treatment crossover (RPSFTM and subgroup analyses) showed a superior survival benefit compared to the ITT analysis.
- As of the July 2020 cutoff, the median observed survival of 25.8 months in those initially randomized to AMX0035 compared to the RPSFTM-adjusted median survival of 15.2 months in those initially randomized to placebo, a difference of 10 .6 months, with a HR of 0.39 (95% CI 0.17 to 0.88; P =.023).
- The RPSFTM analysis models what the survival outcome of the placebo group would have been had participants not crossed over to AMX0035 in the OLE phase.
- As of the March 2021 deadline, the same RPSFTM analyzes were performed and yielded consistent results.
- As of the July 2020 deadline, post-hoc subgroup assessment based on randomization group as well as enrollment in the OLE phase demonstrated that participants initially randomized to AMX0035 and then enrolled in the OLE phase survived 18.8 months ( P <.0001 longer than participants who never received amx0035.>
“The results of these long-term analyzes from the CENTAUR trial provide further evidence that AMX0035 may provide a survival benefit in people with ALS and provide insight into potential new approaches to analyzing survival data in ALS trials,” said Sabrina Paganoni, MD, Ph.D., principal investigator of the CENTAUR trial, researcher at the Sean M. Healey & AMG Center for ALS at Mass General, and associate professor of PM&R at Harvard Medical School and at Spaulding Rehabilitation Hospital. “As a serious and life-threatening disease, time is invaluable for people living with ALS and their families, and any potential treatment that can offer more time is important.”
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 & 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 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 amylyx.com and follow us on LinkedIn and Twitter. For investors, please visit 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. Such statements include, but are not limited to, statements regarding the potential approval of AMX0035 for the treatment of ALS; the potential of AMX0035 as a treatment for ALS and the potential benefits of administering AMX0035; and expectations regarding our longer-term strategy, including the potential of AMX0035 to treat other neurodegenerative diseases. 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 strategy, regulatory developments, expectations regarding the timing the FDA’s review of 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 the United States Securities and Exchange Commission of Amylyx (SEC), including Amylyx’s Annual Report on Form 10-K for the fiscal year ended December 31, 2021, and subsequent filings with of 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.
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Amylyx Pharmaceuticals, Inc.
KEYWORD: UNITED STATES NORTH AMERICA MASSACHUSETTS
INDUSTRY KEYWORD: ONCOLOGY HEALTH CLINICAL TRIALS RESEARCH SCIENCE PHARMACEUTICALS BIOTECHNOLOGY
SOURCE: Amylyx Pharmaceuticals, Inc.
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PUBLISHED: 05/05/2022 09:56 / DISK: 05/05/2022 09:56