Biogen, Ionis halt ALS drug after study failure

Biogen and Ionis Pharmaceuticals have decided to halt the development of an experimental drug for amyotrophic lateral sclerosis (ALS) following results from a recent clinical trial that didn’t meet their expectations. The drug, named BIIB105, was designed to lower levels of ataxin-2, a protein associated with ALS. The trial, involving nearly 100 participants, demonstrated that the drug effectively reduced ataxin-2 levels over a six-month treatment period. However, it failed to alter the progression of the disease, as it did not impact key health measures like breathing, strength, and overall function. Additionally, BIIB105 did not significantly reduce neurofilament light chain, another protein important in ALS research.

Stephanie Fradette, head of Biogen’s Neuromuscular Development Unit, noted that while BIIB105 successfully lowered ataxin-2 protein, it didn't slow down the disease process, which was evidenced by the lack of reduction in neurofilament levels. Participants who finished the initial trial phase were given the option to continue in an open-label extension phase, where they all received BIIB105. Data from this phase mirrored earlier findings, showing sustained reductions in ataxin-2 but no impact on neurofilament or clinical outcomes. The companies concluded that no subgroup of treated patients showed clinical benefits.

The analysis of the trial data is still ongoing, and Biogen and Ionis plan to present more detailed results at an ALS research convention in Stockholm next month. The discontinuation of BIIB105 development marks another setback in the challenging field of ALS drug development. ALS remains a complex and difficult disease to treat, with only a few approved medications since its discovery over a century ago. This year, the list of available treatments became even shorter when Amylyx Pharmaceuticals withdrew a once-promising medication from the market.

In April 2023, the FDA approved Qalsody, the latest addition to ALS treatments, though it is only effective for a small subset of ALS patients with specific genetic mutations. Biogen and Ionis developed Qalsody using antisense oligonucleotide drugmaking technology. The drug works by disrupting the production of an ALS-associated protein called SOD1. Although Qalsody failed to meet the primary endpoint of its pivotal trial, it did succeed in lowering neurofilament light chain levels, a biomarker of neurological damage. The FDA's approval of Qalsody has opened a new pathway for ALS drugmakers, who now prioritize demonstrating an effect on neurofilament in their trials.

Despite the success with Qalsody, other ALS research efforts by Biogen and Ionis have faced challenges. In 2022, they terminated another antisense drug, BIIB078, after disappointing results in an early-stage trial. Additionally, Ionis announced that Biogen chose not to license a drug they were developing for Angelman syndrome, despite Ionis reporting positive results.

However, the collaboration between Biogen and Ionis has been productive in other areas. They developed Spinraza, a highly successful treatment for a rare muscle-wasting disease. Biogen has also highlighted the potential of another experimental drug, BIIB080, currently in mid-stage testing as a possible treatment for Alzheimer’s disease.