Biogen and Denali End Development of Parkinson’s Drug Candidate BIIB122

Biogen and Denali Therapeutics have announced the conclusion of development for their experimental Parkinson’s disease therapy, BIIB122, also known as DNL151. The decision follows the results of a phase 2b clinical trial, which failed to meet its primary endpoint of slowing the progression of the condition in patients with idiopathic Parkinson’s disease.

Clinical Trial Results

The midphase trial involved 650 subjects and was designed to evaluate the efficacy of the drug in targeting the LRRK2 protein. While the researchers observed more than 90% kinase inhibition of peripheral LRRK2 and a roughly 30% reduction in a cerebrospinal fluid (CSF) biomarker of the kinase’s activity, these biological indicators did not translate into clinical benefits for patients.

According to the companies, the drug candidate demonstrated an acceptable safety profile and was generally well tolerated by participants. However, the absence of efficacy signals across primary and secondary endpoints led the partners to stop development of the program for idiopathic Parkinson’s.

Background on the LRRK2 Program

The partnership between Biogen and Denali began in 2020, with Biogen providing a $400 million upfront payment to collaborate on the LRRK2 program. The scientific rationale for the treatment was based on research linking mutations that increase the activity of the LRRK2 kinase to the aggregation of toxic proteins in the brain, which is a hallmark of Parkinson’s disease progression.

The companies had previously initiated a phase 2 trial in early-stage Parkinson’s and a phase 3 study in a genetic subpopulation. Following the recent data readout, the partners have now moved to discontinue the program.

Key Takeaways

• Trial Failure: BIIB122 failed to slow Parkinson’s disease progression compared to a placebo in a large-scale phase 2b study.
• Biomarker vs. Efficacy: While the drug successfully inhibited the LRRK2 protein as intended, this target engagement did not result in improved clinical outcomes for patients.
• Program Discontinuation: Biogen and Denali have formally ceased development of the candidate for the idiopathic form of the disease.
• Safety Profile: The drug was reported to be well tolerated, despite its lack of therapeutic efficacy in the trial population.

Looking Ahead

The termination of the BIIB122 program represents a significant shift for the collaboration, which had previously been a high-profile effort to address the underlying mechanisms of Parkinson’s disease. As the scientific community continues to study the role of LRRK2, the focus remains on understanding why target engagement did not yield the expected clinical results in this trial. Biogen continues its broader work in neurological diseases, maintaining a portfolio that includes treatments for multiple sclerosis, spinal muscular atrophy, and Friedreich’s ataxia.