Biogen and Ionis Announce Phase 1/2 Results for ALS Drug

Biogen Inc. and Ionis Pharmaceuticals, Inc. have decided to halt the development of BIIB105 (ION541), a promising investigational antisense oligonucleotide (ASO) aimed at treating amyotrophic lateral sclerosis (ALS). This decision is based on the results from the Phase 1/2 ALSpire study. BIIB105 was engineered to decrease the expression of the ataxin-2 (ATXN2) protein and showed a significant reduction in ATXN2 levels in the cerebrospinal fluid (CSF). However, despite this reduction, the treatment did not lead to a decrease in plasma neurofilament light chain (NfL) levels, a key marker of neurodegeneration and neuronal damage, during the six-month placebo-controlled period. Additionally, BIIB105 did not positively impact clinical outcomes related to patient function, breathing, or strength.

Stephanie Fradette, Pharm.D., head of the Neuromuscular Development Unit at Biogen, expressed disappointment, stating that while ATXN2 protein levels were reduced, the absence of NfL reduction indicated that the disease process was not slowed. She acknowledged the invaluable contributions of the study participants and reaffirmed Biogen's commitment to developing effective treatments for ALS.

Frank Bennett, Ph.D., executive vice president and chief scientific officer of Ionis, echoed similar sentiments, appreciating the participants and investigators for their role in the study. He emphasized Ionis’s ongoing dedication to the ALS community, mentioning their Phase 3 ulefnersen program targeting the genetic form of the disease known as FUS-ALS.

The longer-term data from the open-label extension of the study mirrored the findings from the six-month placebo-controlled period. There were sustained reductions in ATXN2 protein but no impact on NfL levels or clinical outcome measures over more than 40 weeks of follow-up. No subgroup, including those with a Poly-CAG expansion in the ATXN2 gene, showed any benefit from the treatment.

The Phase 1/2 study was a rigorous, randomized, placebo-controlled, dose-escalating trial involving 99 adult participants with ALS, who received either BIIB105 or a placebo over three to six months. Those who completed the placebo-controlled period could join an open-label extension. Common adverse events (AEs) among those treated with BIIB105 included procedural pain, headache, and falls. Discontinuation due to AEs was higher in the BIIB105 group (8.3%) compared to the placebo group (3.6%).

Despite discontinuing BIIB105, Biogen remains deeply invested in ALS research. The company has learned from past experiences, including a difficult decision in 2013 to halt a late-stage ALS asset. These learnings have been applied to a robust pipeline focused on genetic and other forms of ALS, with the objective of bringing effective therapies to patients. QALSODY® (tofersen), the first treatment targeting a genetic cause of ALS, discovered by Ionis, is part of this effort. Biogen continues to explore new treatments, particularly addressing TDP43 pathology, a hallmark seen in 97% of ALS cases.

Founded in 1978, Biogen is at the forefront of biotechnology, committed to transforming patients' lives with innovative science and treatments. The company's strategy involves balancing risks and returns to ensure long-term growth and value creation for shareholders and the community.

Ionis Pharmaceuticals has been a pioneer in RNA-targeted therapies for three decades, with a formidable pipeline in neurology, cardiology, and other high-need areas. The company’s dedication to neurology has led to several Phase 3 studies and an array of clinical developments, with a focus on diseases lacking effective treatments, such as ALS. Ionis has successfully developed three commercially available neurological disease medicines, including the first approved treatment for spinal muscular atrophy and QALSODY for SOD1-ALS.