Wolfram Syndrome

- Dr. Zeiher brings more than 20 years of drug development experience in areas with serious unmet treatment needs at companies including Astellas Pharma, Pfizer, Eli Lilly and Company, and Merck CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the addition of Bernhardt G. Zeiher, MD, FCCP, FACP, to its Board of Directors (“Board”). Dr. Zeiher brings more than 20 years of drug development experience where, in his various roles, he oversaw the approval of 15 new treatments that addressed people’s unmet needs in serious diseases with few to no treatment options. Most recently, he served as Chief Medical Officer (“CMO”) of Astellas Pharma, where he led early- and late-stage drug development, medical and regulatory affairs, pharmacovigilance, and quality assurance. “This is a pivotal time for Amylyx, and we are thrilled to welcome Dr. Zeiher to our Board to share his perspectives and expertise as the company continues to build a pipeline supporting our collective mission to one day end the suffering of neurodegenerative diseases,” said George M. Milne, Jr., PhD, Chairman of Amylyx’ Board. “Dr. Zeiher's insights of the intricacies and complexities of drug development and innovation in diseases with clear unmet need will be valuable as we continue to serve neurodegenerative disease communities impacted by these devastating diseases.” Dr. Zeiher is a recognized industry leader who spent more than 10 years at Astellas Pharma, holding multiple roles of increasing responsibility in the drug development division, leading up to his role as CMO from 2018 to 2022. Prior to his time at Astellas, Dr. Zeiher held various roles leading drug development at other pharmaceutical companies including Pfizer, Eli Lilly and Company, and Merck. Dr. Zeiher also practiced medicine at a tertiary medical center in Indianapolis and has held a range of board appointments since 2014, including positions at PhRMA Biomedical Advisory Committee, TransCelerate Biopharma, Biotechnology Innovation Organization, Astellas Global Health Foundation, and most recently, Entrada Therapeutics, which he joined in 2023. “We are seeing a transformation in neurodegenerative diseases, both in potential new treatments and what we’re learning through research, and I believe Amylyx is a catalyst in that change,” said Dr. Zeiher. “The company’s community-centric values, steadfast commitment to following the science, and beyond-therapy approaches and support for the neurodegenerative disease community are a few examples of why I am excited for the future and what we can accomplish to support those living with these devastating diseases and their loved ones.” “Dr. Zeiher brings to the Board his distinguished drug development background in overseeing the approval of 15 medicines, and his first-hand experience as a physician. On behalf of the entire Amylyx team, we are delighted to welcome him onboard as we continue to advance our mission to one day end the suffering caused by neurodegenerative diseases,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “We have several important milestones that we’re working toward this year where Dr. Zeiher’s expertise will be key, including our goal to bring our antisense oligonucleotide AMX0114, developed in-house, to the clinic for ALS, continuing to research the potential of AMX0035 in diseases like Wolfram syndrome and progressive supranuclear palsy, and sharing additional insights, learnings, and next steps from our Phase 3 PHOENIX trial in ALS.” Dr. Zeiher received a B.S. in biology from the University of Toledo and an MD from Case Western Reserve University School of Medicine. He completed his internal medicine residency and chief residency at University Hospitals of Cleveland and then finished his physician training as a Pulmonary and Critical Care Fellow at University of Iowa Hospitals and Clinics. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada, EMEA, and Japan. For more information, visit amylyx.com and follow us on LinkedIn and X, formerly known as Twitter. For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call 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 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, the Company’s expectations of contributions from its board of directors; the Company’s beliefs regarding the benefits of AMX0035 in neurodegenerative diseases; expectations regarding the continued research of AMX0035 in progressive supranuclear palsy and Wolfram syndrome; the Company’s potential announcement of additional insights, learnings, and next steps from the Phase 3 PHOENIX trial; the Company’s expectations with respect to its progress through IND-enabling studies of AMX0114; the Company’s expectations with respect to its early-stage ALS diagnostic test; and expectations regarding the Company’s longer-term strategy. Any forward-looking statements in this press release 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 risks and uncertainties set forth in Amylyx’ filings with the Securities and Exchange Commission (“SEC”), including its Annual Report on Form 10-K for the year ended December 31, 2023, 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. Subject to any obligations under applicable law, 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.

An Amylyx Pharmaceuticals amyotrophic lateral sclerosis drug that won a controversial FDA approval based on mid-stage clinical trial results has failed to meet all of the goals of a larger Phase 3 clinical trial, putting the future of the drug and the company in question. According to preliminary results announced Friday, the drug, Relyvrio, was not better than a placebo at slowing progression of the neuromuscular disorder. The study’s primary endpoint was to show a change in score according to a rating scale used to assess function in ALS patients. Cambridge, Massachusetts-based Amylyx said this result was not statistically significant. The drug also did not achieve statistical significance on secondary goals that include measures of breathing function and quality of life. Detailed results were not disclosed, but the company said data from the clinical trial will be presented at an upcoming medical meeting and published in a medical journal later this year. In the near term, the company has set an eight-week timeline to determine its next steps for Relyvrio. Those steps could include voluntarily withdrawing the drug from the market, co-CEO Justin Klee said, speaking during a Friday conference call. To inform this decision, Klee said the company will share the topline data with the FDA and Health Canada as well as the ALS community. “As we consider our plans, we will be led by two key principles: doing what is right for people living with ALS informed by regulatory authorities and the ALS community, and doing what the science tells us,” Klee said. Shares of Amylyx opened Friday at $2.99 apiece, down more than 82% from Thursday’s closing price. Relyvrio is a fixed-dose combination of two compounds, each targeting a different neurodegenerative disease pathway. Hitting both pathways is intended to reduce cellular stress that contributes to neuronal cell death. The drug achieved positive results in a 137-patient placebo-controlled Phase 2 study that was the basis for its 2022 approval. The FDA had initially asked Amylyx to conduct a larger Phase 3 study to support a regulatory submission. But in explaining its decision to approve Relyvrio based on a single Phase 2 trial, the FDA said it was exercising “regulatory flexibility” due to the life-threatening nature of the disease, which has few treatment options. Relyvrio’s approval was a traditional approval, not an accelerated one. Accelerated approvals require a post-marketing confirmatory clinical trial. But Amylyx remained committed to completing the Phase 3 study, expecting the additional data would be needed in other markets (ahead of the FDA decision, the Amylyx drug was approved in Canada, where it is marketed as Albrioza; European authorities last year issued a negative opinion on drug’s application). During the advisory committee preceding the FDA decision, Klee said Amylyx would withdraw Relyvrio from the market if it failed the larger clinical trial. The Phase 3 study had a design similar to the Phase 2 study and it used the same clinical trial goals. But with four times as many patients evaluated for twice as long, this study was better-powered to detect the drug’s effects. In addition to the measures of function, the study had the additional goal of measuring overall survival. Co-CEO Joshua Cohen said survival data are not yet mature. While detailed results for the primary and secondary endpoints remain undisclosed, Klee said they speak to the heterogeneity of ALS—a single disease can be driven by multiple causes. The results also speak to the challenges of neurodegenerative disorders broadly, he added. Amylyx has been evaluating whether Relyvrio’s approach to protecting neurons can also treat other neurodegenerative diseases. A Phase 3 test is ongoing in progressive supranuclear palsy; preliminary data are expected in 2025 or 2026. A Phase 2 study in Wolfram syndrome is expected to yield preliminary data in the second quarter of this year. The Amylyx pipeline also includes AMX0114, an antisense oligonucleotide targeting a gene that encodes an enzyme associated with neurodegeneration. Cohen said the company hopes to advance this program to the clinic in the second half of this year. In 2023, Relyvrio/Albrioza accounted for $380.7 million in revenue, according to Amylyx’s annual report. While the company evaluates its next steps. the product will continue to be available to patients in the U.S. and Canada, Klee said. Amylyx will no longer promote the drug, but the company’s patient support services will remain in place. Amylyx completed 2023 with $371 million in cash. Chief Financial Officer Jim Frates said Amylyx has the financial resources to focus on its earlier-stage programs, but that work may be under a different company structure. He declined to elaborate, saying “now is not right time to give clear plans.” Image: koto_feja, Getty Images

Amylyx Pharmaceuticals' Relyvrio was the first drug approved for amyotrophic lateral sclerosis and generated sales of $380 million last year. But the company faces tough questions after reporting a failure in a phase 3 confirmatory trial. After reporting the failure of a confirmatory trial of its amyotrophic lateral sclerosis (ALS) drug Relyvrio (AMX0035), Amylyx Pharmaceuticals is uncertain whether it will pull the treatment from the market in the U.S. and in Canada, where it is known as Albrioza. “We’ll spend the next eight weeks engaging with regulatory authorities and the ALS community to share the top-line data,” co-CEO Justin Klee said on a Friday conference call. “We’ll follow the science and do what’s right for the community which may include voluntarily removing the product from the market.” The 11-year-old Cambridge, Massachusetts-based company has decided to pause promotion of Relyvrio. Patient support services will remain in place, it said. Two weeks ago, Amylyx reported sales of Relyvrio at $380 million in its first full year on the market, following its approval in September 2022. While sales initially scaled up quickly, the trajectory had slowed, going from $103 million in the third quarter to $108 million in the fourth quarter. Other than to report that the PHOENIX trial did not meet its primary endpoint, failing to reach statistical significance as measured by change from baseline in the revised ALS functional rating scale (ALSFRS-R), or any of its secondary objectives, Amylyx did not reveal figures from the 48-week trial that enrolled 664 ALS patients. The company said it will present the data at an upcoming medical conference, and results will be published in a medical journal later this year. https://poll.fm/13450529 With the devastating news, Amylyx’s shares plummeted 83% by midmorning. “The news comes as a massive disappointment—not only for us (where AMLX has been a top pick) and investors—but also to ALS patients and the overall ALS community,” analysts from Mizuho Securities wrote in a note to clients. The company said it will continue to study AMX0035 as a treatment for two other neurodegenerative diseases—Wolfram syndrome and progressive supranuclear palsy. Amylyx also hopes to enter the clinic in the second half of this year with AMX0114, a treatment for ALS patients designed to lower their levels of calpain-2 to strengthen their nerve fibers. After much consternation and two advisory committee meetings—one voting down AMX0035 6-4 and the other giving it a thumbs-up vote of 7-2 after new analysis of trial data—the FDA signed off on Relyvrio 19 months ago. The decision was based on results of the phase 2 CENTAUR trial, which showed that AMX0035 slowed progression and functional decline and extended survival. Experts who recommended rejection urged the FDA to wait until results of the phase 3 PHOENIX trial were available. On Friday, Klee would not speculate on the difference between the trial results. “I think it’s early,” Klee said. “It’s particularly important to take time to meet with the ALS experts. I think it speaks to the heterogeneity of ALS and also the difficulty in ALS and neurodegenerative diseases more in general. It’s so imperative that when we all, fighting these diseases, have setbacks like this, we learn from them so we can continue to advance because I do very strongly believe that we can have meaningful advances for people with neurodegenerative diseases." The ALS Association was heavily invested in the success of the drug as well. Through its Ice Bucket Challenge in 2014, the organization donated $2.2 million to assist in its development. It also collected more than 50,000 signatures and submitted them to the FDA in 2020, urging the regulator for approval. "While today's news is disappointing, there are more than 50 potential treatments in the clinical stage of development, including more than a dozen in phase 3 trials," the ALS Association said in a statement. "We are more committed than ever to ensuring that safe and effective treatments are approved and available to people living with ALS as quickly as possible."