Biogen and Denali Discontinue BIIB122 Development in Idiopathic Parkinson's After Phase 2b LUMA Miss

Biogen Inc. and Denali Therapeutics Inc. announced topline results from the Phase 2b LUMA study of BIIB122 (DNL151), an investigational small molecule inhibitor of LRRK2, in individuals with early-stage Parkinson's disease. The study did not meet its primary endpoint: BIIB122 did not slow the progression of Parkinson's disease versus placebo, as measured by Time to Confirmed Worsening in the modified Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and III combined score. Secondary endpoints also did not show a benefit with BIIB122.

Based on these results, Biogen and Denali will discontinue further development of BIIB122 in idiopathic Parkinson's disease. Denali will continue to independently conduct the Phase 2a BEACON study evaluating the small molecule inhibitor in carriers of a pathogenic LRRK2 variant.

LUMA was a Phase 2b multi-center, randomized, double-blind, placebo-controlled study that evaluated BIIB122 compared to placebo in 648 people with early-stage Parkinson's disease between the ages of 30 and 80. Participants received BIIB122 or placebo for a minimum of 48 weeks and up to 144 weeks. The study included individuals with or without a pathogenic LRRK2 variant.

Exploratory biomarker endpoints demonstrated >90% kinase inhibition of peripheral LRRK2 (phosphoserine 935) and, in a cerebrospinal fluid sub-study, up to approximately 30% reduction in a biomarker of LRRK2 activity (phosphorylated Rab10). Expected levels of BIIB122 in the blood and CSF were sustained across the study. BIIB122 was generally well tolerated with an acceptable safety profile.

The senior vice president and head of neurodegeneration clinical development at Biogen stated: "While these are not the results we hoped for, these data provide important information to the Parkinson's community and will be presented at an upcoming scientific conference." Denali's chief medical officer and head of development said: "While we are disappointed with these results, we believe the LUMA study was a robust test of LRRK2 inhibition using BIIB122 in idiopathic Parkinson's disease and there is more to be learned about LRRK2 as a potential therapeutic target." He also noted that Denali continues to study the inhibitor in the Phase 2a BEACON study in individuals confirmed by genetic testing to be carriers of a pathogenic LRRK2 variant, which is associated with increased LRRK2 kinase activity.

The global Phase 2a BEACON study is designed to assess safety, pharmacokinetics and biomarkers of lysosomal pathway engagement, which will inform the biomarker profile in LRRK2 pathogenic variant carriers and the impact of LRRK2 inhibition. Data from BEACON are anticipated in the first half of 2027. The BEACON study is being operationalized by Denali and funded under a Collaboration and Development Funding Agreement between Denali and a third party.

Biogen and Denali will share detailed findings from the LUMA study at an upcoming scientific conference to contribute to the broader understanding of Parkinson's disease and LRRK2 biology.

Parkinson's disease is a progressive neurodegenerative disorder that affects movement and a wide range of non-motor functions. An estimated one million people in the U.S. and more than 10 million people worldwide have the disease.