Phase 3 Trial of LRRK2 Inhibitor Being Initiated for Parkinson Disease

The phase 3 LIGHTHOUSE study (NCT05418673) to evaluate a small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2)(BIIB122/DNL151; Biogen, South San Francisco, CA)(Denali, Cambridge, MA) in participants with LRRK2-related Parkinson disease (PD) has been initiated. In this trial, approximately 400 participants will be treated with the LRRK2 inhibitor or placebo. All participants must test positively for the leucine-rich repeat kinase 2 (LRRK2) gene mutation. Mutations LRRK2 account for 4-5% of familial and 1-2% of sporadic PD. 

“Mutations in the LRRK2 gene comprise the most frequent mutations found in PD, indicating that LRRK2 inhibition may be a promising therapeutic approach to the disease,” said Samantha Budd Haeberlein, PhD, 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 PD caused by a LRKK2 mutation.”

The study will measure whether there is worsening of disease by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) for up to 180 weeks.  In phase 1a and 1b clinical trials, target engagement and reduction in relevant biomarkers was observed. Phase 2 trials are ongoing with no data yet released.

“In collaboration with Biogen, we are excited to be pursuing the potential of LRRK2 inhibition as an effective treatment for PD,” stated Carole Ho, MD, 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 PD, we hope to have the opportunity to bring a novel therapeutic option to people living with PD.”