Biogen and Ionis Halt BIIB105 Program in ALS Setback

In a familiar and disappointing outcome, Biogen and Ionis Pharmaceuticals have abandoned another drug aimed at treating amyotrophic lateral sclerosis (ALS). The latest drug, BIIB105, an antisense oligonucleotide designed to reduce the expression of the ataxin-2 (ATXN2) protein thought to be involved in ALS, failed to deliver promising results in clinical studies. This decision comes after an unsatisfactory performance in the Phase I/II ALSpire study, which included 99 adults diagnosed with ALS.

During the six-month, placebo-controlled study period, BIIB105 did not achieve a reduction in plasma neurofilament light chain (NfL) levels, a critical biomarker for neurodegeneration and neuronal damage. Additionally, the treatment showed no significant impact on clinical measures such as functional ability, respiratory function, or muscle strength. While longer-term data revealed sustained reductions in ATXN2 levels, these reductions did not translate into changes in NfL or observed clinical outcomes over a period exceeding 40 weeks. No subgroup, including those with Poly-CAG expansion in the ATXN2 gene, demonstrated any benefit.

Stephanie Fradette, who leads neuromuscular development at Biogen, commented, "While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which gives us confidence that BIIB105 did not slow the disease process." The study also reported a higher incidence of adverse events leading to dropouts in the BIIB105 group (8.3%) compared to the placebo group (3.6%).

Despite these setbacks, Biogen and Ionis plan to present the ALSpire study data at the upcoming European Network to Cure ALS (ENCALS) meeting in June. This recent failure adds to a series of disappointments in the ALS research field for both companies. In 2022, they terminated the ALS candidate BIIB078, another antisense drug targeting C9orf72 mutations, after it failed to meet key efficacy goals in a Phase I study. Subsequently, Biogen also discontinued BIIB100, an XPO1 inhibitor known as KPT-350, part of a collaboration with Karyopharm Therapeutics worth up to $217 million.

Nevertheless, there have been occasional successes. Last year, Biogen achieved an FDA accelerated approval for Qalsody (tofersen) for the rare SOD1 genetic form of ALS. Despite this, the broader ALS patient population continues to await an effective disease-modifying therapy. Earlier this year, Amylyx Pharmaceuticals fulfilled its commitment to withdraw the ALS drug Relyvrio (sodium phenylbutyrate/taurursodiol) from the market after it failed the confirmatory PHOENIX trial.

In a separate statement, Biogen disclosed its decision not to proceed with licensing and developing BIIB121 (ION582), another antisense oligonucleotide from Ionis designed for patients with Angelman syndrome. This decision was made despite positive findings from the Phase I/IIa HALOS study, which showed promising and consistent benefits in areas such as cognition, communication, and motor function. Ionis’ CEO, Brett Monia, expressed optimism about advancing ION582 into a pivotal study.

The decision to abandon BIIB121 raised some eyebrows among analysts at Stifel Nicolaus, who noted the scarcity of promising opportunities in Biogen’s pipeline. However, they acknowledged there were many unknowns due to the lack of detailed data in Ionis' announcement, speculating that the benefit magnitude of BIIB121 over the natural history in the study might not have been substantial.