Biogen and Denali Therapeutics halt development of BIIB122 for idiopathic Parkinson's after Phase 2b trial misses goals

Pharmaceutical companies Biogen and Denali Therapeutics have announced that their Phase 2b LUMA study evaluating the drug candidate BIIB122 did not meet its primary or secondary targets. The clinical trial focused on testing the safety and effectiveness of the drug in 648 people with early-stage Parkinson's. Because the treatment failed to show a benefit in slowing down the progression of the condition compared to a placebo, the companies have decided to discontinue the clinical development of BIIB122 for individuals with idiopathic Parkinson's, which is the form of the condition where the exact cause is unknown. The drug candidate BIIB122 works by blocking the activity of an enzyme called LRRK2. Research has shown that overactive LRRK2 can disrupt the endolysosomal system, which serves as the waste disposal mechanism within brain cells. When this disposal system fails, harmful proteins can accumulate and lead to cell damage. The LUMA study successfully demonstrated that the drug could effectively block this enzyme and reduce related biomarkers in the blood and spinal fluid, but this biochemical change did not translate into a meaningful clinical benefit for the participants. The progression of the condition was measured using a standardized rating scale that evaluates daily living experiences and motor experiences, and no significant difference was found between those taking the drug and those taking the placebo. Despite the setback for the wider Parkinson's community, the development of the drug is not stopping entirely. Denali Therapeutics will continue to independently run a separate Phase 2a clinical trial called the BEACON study. This ongoing trial is specifically testing BIIB122 in individuals who are confirmed through genetic testing to carry a pathogenic mutation in the LRRK2 gene, which is directly linked to increased enzyme activity. Because these individuals have a clear genetic driver for their condition, researchers hope the therapeutic approach might still offer benefits for this specific group. Results from the BEACON study are expected in the first half of 2027, and detailed data from the unsuccessful LUMA trial will be shared at a future medical conference to help guide future research into the biology of the condition.