Supranuclear Palsy, Progressive

Amylyx Pharmaceuticals will withdraw Relyvrio (sodium phenylbutyrate/taurursodiol) from the US market, following through on a commitment made when the amyotrophic lateral sclerosis (ALS) therapy controversially won accelerated approval in 2022. At that time, joint CEO Justin Klee said such a move would be likely if a confirmatory study failed – the company announced last month that the PHOENIX trial was a dud.Klee, along with joint CEO Joshua Cohen, said Thursday that the decision to withdraw Relyvrio was “reached…in partnership with the stakeholders who will be impacted.” Amylyx, which will also pull the drug in Canada, where it is sold as Albrioza, noted that it will provide the therapy free of charge for those currently on treatment who want to continue.Staff losses of 70%The drugmaker will also cut around 70% of its workforce as part of a restructuring plan as it looks to prioritise resources, extending its cash runway into 2026. Amylyx is also investigating the oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol - known as AMX0035 - in Wolfram syndrome and progressive supranuclear palsy (PSP). Interim data from the Phase II HELIOS trial of AMX0035 for the treatment of Wolfram syndrome are expected later this month.Meanwhile, chief medical officer Camille Bedrosian, noted that the Phase III ORION study of AMX0035 for PSP is ongoing, with “an interim analysis…now expected in mid-2025.” Amylyx has also not given up on ALS, with AMX0114, an antisense oligonucleotide targeting calpain-2, set to enter clinical studies in the second half of the year.For related analysis, read KOL Views Q&A: Leading neurologist outlines where ALS field goes next after Amylyx’s Relyvrio failure.

Pictured: Illustration showing a neuron being destroyed/iStock, Dr_Microbe Amylyx Pharmaceuticals on Thursday announced that it has started the process of pulling its amyotrophic lateral sclerosis drug Relyvrio (sodium phenylbutyrate and taurursodiol) from the U.S. and Canadian markets and will reduce the company’s workforce by approximately 70% under a restructuring plan. Effective Thursday, Relyvrio will no longer be available for new patients. Those who are currently being treated with Relyvrio can either stay on treatment or transition into a free program, depending on their physician’s advice, according to the company. Amylyx said it will work with the FDA and Health Canada to terminate the marketing authorizations for Relyvrio in these countries. Joshua Cohen and Justin Klee, co-CEOs of Amylyx, in a statement called the withdrawal of Relyvrio a “difficult moment” for the company and for patients with amyotrophic lateral sclerosis (ALS). “The decision to remove Relyvrio from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community,” Cohen and Keel said. Last month, Relyvrio failed its highly anticipated Phase III PHOENIX trial, unable to significantly improve scores in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale at 48 weeks versus placebo. Amylyx’s drug also fell short of its secondary endpoints, including slow vital capacity and self-reported health status, as measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire. Amylyx will present data from PHOENIX at the upcoming American Academy of Neurology meeting, according to Thursday’s announcement. The study’s open-label extension phase is also ongoing, and Amylyx plans to collect survival data from the trial to help inform future studies in ALS. Losing its only commercial product, Amylyx on Thursday also launched a sweeping restructuring initiative to cut costs and optimize the use of its resources, with an eye toward upcoming clinical milestones. The biotech will lay off around 70% of its employees and lower financial commitments outside of its new priority areas. Amylyx will now focus on its lead asset AMX0035—which, like Relyvrio, also contains sodium phenylbutyrate and taurursodiol—being developed for Wolfram syndrome and progressive supranuclear palsy. The biotech is also advancing the antisense oligonucleotide candidate AMX0114 in ALS. CMO Camille Bedrosian revealed in a statement that Amylyx will present Phase II data for AMX0035 in Wolfram syndrome later this month while its Phase III ORION study in progressive supranuclear palsy is set for an interim analysis in mid-2025. The biotech is also preparing to initiate a clinical trial for AMX0114 in the second half of 2024. The company restructuring and priority changes should extend Amylyx’s cash runway into 2026, according to the announcement. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Amylyx Pharmaceuticals is discontinuing its ALS treatment, Relyvrio, after phase 3 trial results failed to demonstrate the drug’s efficacy. Just last month, the drugmaker shared disappointing results from a confirmatory study on Relyvrio, which failed to meet primary or secondary goals. The phase 3 PHOENIX trial, involving 664 adults with ALS, did not achieve statistical significance in changing the revised ALS functional rating scale after 48 weeks. Relyvrio's approval in 2022 followed a notable reversal by an FDA advisory committee, which endorsed the drug on its second review. The medication, combining sodium phenylbutyrate and taurursodiol, is designed to protect neurons by blocking pathways that cause cell death, and it can be used alone or with other treatments. Previous studies had shown Relyvrio could slow physical decline in ALS patients, representing a breakthrough in treating this neurodegenerative condition. But this week, the company announced that it will stop offering the treatment to new patients immediately and will allow existing patients to continue receiving the drug for free. In a way, the writing has been on the wall all along. Despite securing approval, Relyvrio's regulatory journey was fraught with challenges even after receiving its nod from the agency. In February of last year, health insurance giant Cigna decided not to cover the drug , calling it “experimental, investigational and unproven.” Adding insult to injury, a few months later Relyvrio faced rejection (for the second time) by the European Union's medicines regulator. To pile on the bad news, Amylyx also revealed its plans to reduce its workforce by 70% to allocate resources towards its main clinical and preclinical programs, aiming to extend its cash runway into 2026. These programs include ongoing research into AMX0035 for Wolfram syndrome and progressive supranuclear palsy (PSP), as well as AMX0114 for ALS. Despite the withdrawal of Relyvrio, Amylyx hopes to focus on treatments that target endoplasmic reticulum stress and mitochondrial dysfunction.