Biogen and Ionis Announce Topline Phase 1/2 Study Results of Investigational Drug in Amyotrophic Lateral Sclerosis

• Development of BIIB105, an investigational antisense oligonucleotide for amyotrophic lateral sclerosis (ALS), will be discontinued based on data from the Phase 1/2 ALSpire study
• Biogen and Ionis continue their long-standing commitment to developing therapies for ALS given the devastating impact of this progressive, fatal neurodegenerative condition

CAMBRIDGE, Mass. and CARLSBAD, Calif., May 16, 2024 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) and Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced the decision to terminate development of BIIB105 (ION541) an investigational antisense oligonucleotide (ASO) for amyotrophic lateral sclerosis (ALS) based on topline results from the Phase 1/2 ALSpire study. BIIB105 was designed to reduce expression of ataxin-2 (ATXN2) protein and demonstrated statistically significant cerebrospinal fluid (CSF) ATXN2 protein reductions in the study. However, over the 6-month placebo-controlled period, treatment with BIIB105 did not result in a reduction in levels of plasma neurofilament light chain (NfL), a marker of neurodegeneration and neuronal damage. Additionally, BIIB105 did not demonstrate an impact on clinical outcome measures of function, breathing, and strength.

“While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which gives us confidence that BIIB105 did not slow the disease process,” said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen. “We are deeply grateful for the contributions of the study participants and remain committed to developing treatments that can meaningfully change the disease trajectory for people living with ALS.”

“We are very appreciative of the people with ALS and investigators who participated in this study and were critical to advancing our scientific understanding of ALS,” said Frank Bennett, Ph.D., executive vice president and chief scientific officer of Ionis. ”Ionis continues to be committed to the ALS community and is advancing our Phase 3 ulefnersen program for people with the genetic form of the disease known as FUS-ALS.”

Longer-term biomarker and efficacy data from the open-label-extension were similar to those seen during the 6-month placebo-controlled treatment period, with sustained reductions in ATXN2 but no impact on NfL or clinical outcome measures over 40+ weeks of follow up. No evidence of benefit was observed in any subgroup evaluated, including those participants with a Poly-CAG expansion in the ATXN2 gene.