Biogen & Denali Therapeutics Announce Initiation of Phase 3 LIGHTHOUSE Study in Parkinson’s Disease Associated With LRRK2 Pathogenic Mutations

Biogen Inc. and Denali Therapeutics Inc. recently announced 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, 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 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, 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 Parkinson’s disease, we hope to have the opportunity to bring a novel therapeutic option to people living with Parkinson’s disease.”

More information about LIGHTHOUSE (NCT05418673) is available at ClinicalTrials.gov.

Following discovery of the LRRK2 mutation as a pathogenic genetic factor for Parkinson’s disease, further research has uncovered that it has the potential to be a novel therapeutic target for Parkinson’s disease. Mutations in leucine-rich repeat kinase 2 (LRRK2) account for 4%-5% of familial and 1%-2% of sporadic Parkinson’s disease.

BIIB122 is a selective, central nervous system-penetrant small molecule inhibitor of LRRK2 that is hypothesized to improve lysosomal dysfunction. BIIB122 is an investigational drug that is not approved by any regulatory authority, and its safety and efficacy have not been established.

As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities. For more information, visit www.biogen.com.

Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For more information, visit www.denalitherapeutics.com.