Biogen, Ionis halt ALS drug development

Biogen and Ionis Pharmaceuticals have decided to discontinue the development of BIIB105, an experimental antisense oligonucleotide intended for treating amyotrophic lateral sclerosis (ALS). This decision follows the results from a phase 1/2 clinical trial known as the ALSpire study.

The primary objective of the ALSpire study was to evaluate the effectiveness of BIIB105 in reducing the expression of ataxin-2 (ATXN2) protein in cerebrospinal fluid. ATXN2 is considered a significant factor in ALS progression. Although BIIB105 successfully lowered ATXN2 levels, it did not reduce the levels of plasma neurofilament light chain (NfL), a biomarker associated with neurodegeneration. Furthermore, the treatment did not lead to improvements in patients' clinical outcomes, such as motor function, respiratory capability, or muscle strength.

The ALSpire study was carefully designed as a randomized, placebo-controlled trial with 99 adult participants diagnosed with ALS. These patients were administered either BIIB105 or a placebo for a period ranging from 3 to 6 months, followed by an open-label extension phase. Among the adverse events reported for BIIB105 were procedural pain, headaches, and falls. Patients receiving BIIB105 experienced a higher rate of discontinuation due to adverse events compared to those in the placebo group. Despite ongoing treatment for over 40 weeks, there was no significant impact on NfL levels or clinical outcomes, although the reduction of ATXN2 was sustained.

In contrast to the disappointing results with BIIB105, Biogen and Ionis had previously achieved a milestone with another antisense oligonucleotide named Qalsody. Last year, Qalsody received FDA approval for treating a rare form of ALS linked to a mutation in the superoxide dismutase 1 (SOD1) gene. This genetic mutation affects approximately 330 individuals in the United States. Qalsody works by blocking the production of the SOD1 protein, preventing its aggregation and the subsequent damage to the nervous system. It stands out as the first approved treatment that targets a genetic cause of ALS.

The decision to halt the development of BIIB105 underscores the complexities and challenges associated with finding effective treatments for ALS. While the reduction in ATXN2 levels was a positive outcome, the lack of impact on crucial biomarkers like NfL and the absence of clinical improvements in patients led to the discontinuation of the program. This also highlights the rigorous evaluation process that potential treatments undergo to ensure they bring meaningful benefits to patients.

Biogen and Ionis continue to focus on other therapeutic avenues and treatments that hold promise for ALS patients. The success of Qalsody represents a significant step forward in the fight against ALS, offering hope for those affected by the disease. Despite the setback with BIIB105, the ongoing research and development efforts by these biopharmaceutical companies remain crucial in the quest to address and ultimately cure ALS.