Amylyx Pharmaceuticals Announces Formal Intention to Remove RELYVRIO®/ALBRIOZA™ from the Market; Provides Updates on Access to Therapy, Pipeline, Corporate Restructuring, and Strategy
- The decision to discontinue RELYVRIO/ALBRIOZA was based on Phase 3 PHOENIX trial results.
- Patients currently on therapy in the U.S. and Canada can transition to a free drug program.
- Amylyx is advancing AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS.
- Interim data from the Phase 2 HELIOS trial of AMX0035 for Wolfram syndrome is expected soon.
- A restructuring plan reduces the workforce by 70% to extend cash runway into 2026.
- None.
The voluntary discontinuation of RELYVRIO/ALBRIOZA by Amylyx Pharmaceuticals marks a significant pivot in the company's strategy, reflecting the complex nature of drug development within the biotech industry. The decision, based on the Phase 3 PHOENIX trial results, underscores the importance of clinical trial outcomes in determining a drug's market viability. This development is likely to have a material impact on Amylyx's revenue projections and could influence investor sentiment.
From a financial perspective, the shift to providing the drug free of charge to current patients might alleviate immediate backlash but will also eliminate a revenue stream. The company's restructuring plan, which includes a workforce reduction of approximately 70%, suggests a strategic realignment to conserve cash and focus on the development pipeline. The extended cash runway into 2026 indicates a short-term financial stabilization, but the reduction in workforce raises concerns about the company's ability to execute on its clinical programs effectively.
The cessation of RELYVRIO/ALBRIOZA for new ALS patients will have a direct impact on treatment options within the neurodegenerative disease space. As a drug targeting endoplasmic reticulum stress and mitochondrial dysfunction, its removal from the market highlights the challenges in treating complex diseases like ALS. The ongoing open-label extension of the PHOENIX trial and the continued investigation into AMX0035 for other conditions such as Wolfram syndrome and progressive supranuclear palsy (PSP) reflect a commitment to understanding neurodegenerative pathways more deeply.
For patients and healthcare providers, the transition to a free drug program for existing patients may provide some continuity of care, but the long-term implications for treatment efficacy and patient outcomes remain uncertain. Amylyx's continued research into AMX0114, targeting calpain-2, suggests an ongoing search for novel therapeutic targets within the ALS treatment landscape.
Amylyx's engagement with regulatory authorities, such as the FDA and Health Canada, in the voluntary discontinuation process demonstrates the regulatory complexities inherent in the pharmaceutical industry. The company's proactive approach in consulting with stakeholders, including the ALS community, before making the decision to withdraw RELYVRIO/ALBRIOZA, is indicative of the ethical considerations and patient-centric focus required in such scenarios.
Legal implications of this decision may involve managing contractual obligations with suppliers and partners, as well as addressing potential liabilities associated with discontinuing a marketed drug. Moreover, the transition of patients to a free drug program must be carefully managed to comply with healthcare regulations and to ensure that patients' rights and access to treatment are maintained.
- Based on topline results from the Phase 3 PHOENIX trial of AMX0035 in ALS, Amylyx has started a process with the FDA and Health Canada of voluntarily discontinuing the marketing authorizations for RELYVRIO/ALBRIOZA
- RELYVRIO/ALBRIOZA will no longer be available for new patients as of today; Patients currently on therapy in the
- Amylyx continues to advance AMX0035 in Wolfram syndrome and in progressive supranuclear palsy (PSP), and AMX0114 in ALS
- Interim data from the Phase 2 HELIOS trial of AMX0035 for the treatment of Wolfram syndrome are expected this month and will be presented during a webcast on April 10, 2024
- Restructuring plan reduces workforce by approximately
“While this is a difficult moment for the ALS community, we reached this path forward in partnership with the stakeholders who will be impacted and in line with our steadfast commitment to people living with ALS and other neurodegenerative diseases. The decision to remove RELYVRIO/ALBRIOZA from the market and provide therapy free of charge for those who wish to continue was informed by the
Amylyx will continue to evaluate and share learnings from
As part of the Company’s purpose to discover and develop innovative new treatment options for neurodegenerative diseases, Amylyx continues to advance two key programs investigating its lead asset AMX0035 in Wolfram syndrome and progressive supranuclear palsy (PSP), and AMX0114, an antisense oligonucleotide targeting calpain-2, in ALS.
“Our pipeline is supported by compelling clinical and preclinical science demonstrating the potential of AMX0035 and AMX0114 in neurodegenerative diseases. AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. We are investigating AMX0035 in diseases where these two pathways are implicated, which includes Wolfram syndrome and progressive supranuclear palsy,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “We look forward to presenting interim data from our Phase 2 HELIOS study of AMX0035 in Wolfram syndrome, a rare, genetic, fatal neurodegenerative disease with no FDA-approved treatment options, later this month. In addition, our Phase 3 ORION study remains ongoing to evaluate AMX0035 for the treatment of progressive supranuclear palsy, a rare neurodegenerative disorder characterized as a tauopathy. We continue to plan for an interim analysis to evaluate the data from ORION that is now expected in mid-2025.”
Dr. Bedrosian continued, “We also remain focused on ALS and believe AMX0114 has strong potential for the treatment of ALS and other diseases. Calpain-2 is considered an essential protein in the process of axonal degeneration and has been repeatedly linked to neurofilament biology in published studies. In our preclinical studies of AMX0114 and in multiple independent published studies, inhibition of calpain-2 has reduced cell death and degeneration and decreased neurofilament levels. We expect to initiate a clinical trial studying AMX0114 in ALS in the second half of this year.”
Amylyx also announced a restructuring to focus the Company’s financial resources on upcoming clinical milestones. The Company will reduce its workforce by approximately
“We are so thankful and grateful to our Amylyx team for their contributions and steadfast dedication,” said Cohen and Klee. “Together, the work we have accomplished across the world has helped build a vital foundation to achieve our mission of one day ending the suffering caused by neurodegenerative diseases, which continue to have critical, unaddressed needs.”
HELIOS Interim Data in Wolfram Syndrome Investor Webcast Details
Amylyx will host a virtual webcast with Dr. Fumihiko Urano, Principal Investigator of the Phase 2 HELIOS clinical trial in Wolfram syndrome and Professor Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine, to discuss interim HELIOS data on April 10, 2024, at 1:30 p.m. ET. A live webcast of the presentation can be accessed under “Events and Presentations” in the Investor section of the Company’s website, https://investors.amylyx.com/news-events/events, and will be available for replay for 90 days following the event.
About AMX0035
AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the
About AMX0114
AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in induced pluripotent stem cell (iPSC)-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations.
About ALS
Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than
About the HELIOS Trial
The HELIOS trial (NCT05676034) is a 12-participant, open-label, proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome.
About Wolfram Syndrome
Wolfram syndrome is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggests that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome. The prognosis of Wolfram syndrome is poor, and many people with the disease die prematurely with severe neurological disabilities.
About the ORION Trial
The ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations.
About PSP
Progressive supranuclear palsy (PSP) is a sporadic, rare, and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP.
PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial, with several genetic and environmental factors likely contributing to tau dysfunction and aggregation.
Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress, and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation.
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
Forward-Looking Statements
Statements contained 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 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, Amylyx’ expectations regarding: interactions with regulatory authorities; the availability of RELYVRIO/ALBRIOZA for patients currently taking RELYVRIO/ALBRIOZA; the timing and significance of learnings from the
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Source: Amylyx Pharmaceuticals, Inc.
