Ionis and Biogen halt ALS drug after Phase I/II failure

The development of new treatments for amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disease, faces yet another obstacle as Ionis and Biogen discontinue their experimental ALS treatment. Their investigational drug, BIIB105, did not show clinical benefits in a Phase I/II trial involving 99 patients, known as the ALSpire study (NCT04494256). Despite significant reductions in the ataxin-2 (ATXN2) protein, the drug did not improve neurodegeneration or functional measures, such as breathing.

ALS, characterized by muscle weakness and paralysis, continues to challenge researchers. Last month, Amylyx Pharmaceuticals pulled its ALS drug, Relyvrio (AMX0035), from the market after a Phase III trial did not meet its endpoints, further underscoring the difficulty in developing effective treatments.

Nevertheless, Ionis and Biogen are not giving up on ALS research. Their other ALS candidate, Qalsody (tofersen), received accelerated approval from the US Food and Drug Administration (FDA) in April 2023. This approval was based on the drug's ability to reduce plasma neurofilament light (NfL) levels, a biomarker associated with nerve injury and neurodegeneration, although it failed a Phase III trial in 2021. The FDA advisory committee recommended conditional approval but voted against full approval at the time.

According to GlobalData's Pharmaceutical Intelligence Centre, Qalsody is projected to generate global sales of $127 million by 2030. The field of ALS research remains active, with ongoing efforts to bring new therapies to market.

Further developments include BrainStorm Cell Therapeutics, which plans to initiate a Phase IIIb confirmatory trial for its ALS candidate, NurOwn (debamestrocel), following a prior Phase III setback. The FDA has provided a special protocol assessment (SPA) for the design of this trial, offering a structured path forward for the stem cell therapy.

Currently, only two drugs are approved for ALS treatment: Mitsubishi Tanabe’s Radicava (edaravone) and the generic drug riluzole. According to a GlobalData report, there will be 74,614 ALS cases in major markets, including the UK, US, Spain, Germany, Italy, France, Japan, and Canada.

Despite the challenges faced in recent trials, the search for effective ALS treatments continues. Stephanie Fradette, head of Biogen's neuromuscular development unit, emphasized that while BIIB105 successfully reduced ATXN2 protein, it did not lower neurofilament levels, indicating that it did not slow disease progression. The quest for disease-modifying therapies in the ALS space remains a priority as the scientific community strives to find solutions for this relentless condition.