Biogen and Ionis Pharmaceuticals 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 six-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.
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.
The Phase 1/2 study was a randomised, placebo-controlled, dose-escalating trial to evaluate BIIB105 administered intrathecally to adults (n=99) with ALS. Participants were randomised to receive BIIB105 or placebo (3:1 or 2:1 ratio) for 3 to 6 months. Participants who completed the placebo-controlled period were eligible to enroll in the open-label extension.
During the six-month placebo-controlled portion of the study, the most common adverse events (AEs) in BIIB105 treated participants were procedural pain, headache and fall. AEs leading to study discontinuation were higher in the BIIB105 group (8.3 per cent) compared with the placebo group (3.6 per cent).
Analyses of data from the study are ongoing to further understand the underlying disease process and effects of BIIB105. The companies will present the BIIB105 Phase 1/2 data at the upcoming European Network to Cure ALS (ENCALS) meeting in Stockholm, Sweden in June.