Ionis and Biogen Reveal Phase 1/2 Study Results for ALS Drug

Ionis Pharmaceuticals and Biogen have decided to halt the development of BIIB105 (ION541), an investigational antisense oligonucleotide (ASO) aimed at treating amyotrophic lateral sclerosis (ALS). This decision follows the results from the Phase 1/2 ALSpire study, which failed to meet critical efficacy benchmarks.

BIIB105 was designed to reduce the expression of the ataxin-2 (ATXN2) protein. While the study showed statistically significant reductions in ATXN2 protein in cerebrospinal fluid, it did not show a reduction in plasma neurofilament light chain (NfL) levels. NfL serves as a marker for neurodegeneration and neuronal damage. Furthermore, BIIB105 did not demonstrate any significant impact on clinical outcomes related to patient function, breathing, and strength.

Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen, expressed gratitude for the study participants' contributions but acknowledged that the lack of impact on neurofilament levels suggests BIIB105 did not slow the disease progression. Frank Bennett, Chief Scientific Officer at Ionis, also extended appreciation to the participants and reiterated Ionis’ commitment to advancing scientific understanding and treatments for ALS.

The Phase 1/2 ALSpire study was a randomized, placebo-controlled trial involving 99 adult participants with ALS. Participants received BIIB105 or a placebo for three to six months in a dose-escalating manner. Following the placebo-controlled period, participants had the option to join an open-label extension study. Over a follow-up period of 40+ weeks, the longer-term data mirrored the initial findings, showing consistent reductions in ATXN2 but no impact on NfL levels or clinical outcomes. No benefits were observed in any specific subgroups, including those with a Poly-CAG expansion in the ATXN2 gene.

Adverse events in the study were more common among those receiving BIIB105, with procedural pain, headache, and falls being the most frequently reported. A higher percentage of BIIB105 participants discontinued the study due to adverse events compared to the placebo group.

Despite the discontinuation of BIIB105, Biogen and Ionis remain committed to ALS research. Biogen has a history of investing in ALS research and continues to apply lessons learned from past experiences to its portfolio of assets focused on both genetic and other forms of ALS. The company is also working on addressing TDP43 pathology, which is a hallmark seen in 97% of ALS cases.

Ionis, on the other hand, continues to advance its Phase 3 program for ulefnersen, targeting a genetic form of ALS known as FUS-ALS. The company has a robust pipeline in neurology and is working on developing treatments for various neurological diseases, including Alzheimer's and Parkinson's, as well as rare conditions like Alexander disease.

Both companies plan to present the detailed data from the BIIB105 Phase 1/2 study at the upcoming European Network to Cure ALS (ENCALS) meeting in Stockholm, Sweden, in June. The continued analysis of the study data aims to enhance the understanding of ALS and the effects of BIIB105.

Ionis Pharmaceuticals, known for its pioneering work in RNA-targeted medicines, continues to innovate in RNA therapies and gene editing. The company has a leading pipeline in neurology and cardiology and remains focused on delivering life-changing advancements for patients.

Biogen, founded in 1978, is a biotechnology company committed to advancing ALS research and delivering new medicines. The company applies a deep understanding of human biology to develop first-in-class treatments that offer superior outcomes. Biogen maintains a robust discovery pipeline and continues to invest in research to bring potential therapies to patients in need.