Biogen and Denali Therapeutics Announce Initiation of the Phase 3 LIGHTHOUSE Study in Parkinson’s Disease Associated with LRRK2 Pathogenic Mutations

Biogen Inc. and Denali Therapeutics Inc. announced that dosing has commenced in the global Phase 3 LIGHTHOUSE study to evaluate the efficacy and safety profile of BIIB122 (DNL151), as compared to placebo in approximately 400 participants with Parkinson’s disease and a confirmed pathogenic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene.

The primary endpoint of the LIGHTHOUSE study is time to confirmed worsening, as assessed using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) over the treatment period, up to 180 weeks. Participants will be randomized to receive oral BIIB122 or placebo once daily.

“Mutations in the LRRK2 gene comprise the most frequent mutations found in Parkinson’s disease, indicating that LRRK2 inhibition may be a promising therapeutic approach to the disease,” said Samantha Budd Haeberlein, Ph.D., Head of Neurodegeneration Development at Biogen. “The LIGHTHOUSE study will specifically recruit individuals with a pathogenic mutation in LRRK2, enabling us to test the genetic hypothesis and implicated lysosomal pathway. The LIGHTHOUSE study is the largest study ever undertaken in individuals with Parkinson’s disease caused by a LRKK2 mutation.”

BIIB122 is an investigational small molecule inhibitor of LRRK2 that was discovered and initially developed by Denali. Denali and Biogen are co-developing and co-commercializing BIIB122 for the potential treatment of Parkinson’s disease.

“In collaboration with Biogen, we are excited to be pursuing the potential of LRRK2 inhibition as an effective treatment for Parkinson’s disease,” said Carole Ho, M.D., Chief Medical Officer of Denali. “The initiation of the Phase 3 LIGHTHOUSE study marks an important milestone in the BIIB122 development program. Together with the recent initiation of the Phase 2b LUMA study in early-stage Parkinson’s disease, we hope to have the opportunity to bring a novel therapeutic option to people living with Parkinson’s disease.”