Denali Therapeutics & Biogen Announce Initiation of Phase 2b Study of LRRK2 Inhibitor in Parkinson’s Disease

Denali Therapeutics Inc. and Biogen Inc. recently announced that dosing has commenced in the global Phase 2b LUMA study to evaluate the efficacy and safety of BIIB122 (DNL151), as compared to placebo in approximately 640 participants with early-stage Parkinson’s disease.

LUMA is a Phase 2b multi-center, randomized, double-blind, placebo-controlled study to evaluate safety and efficacy of BIIB122 in people with early stage Parkinson’s disease between the ages of 30 and 80. The primary endpoint of LUMA is Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) parts II and III combined score over the treatment period. Participants will be randomized to receive oral BIIB122 or placebo once daily.

“More than 10 million people worldwide are affected by Parkinson’s disease, and there is a significant medical need for therapies to slow or stop the progression of this devastating neurodegenerative disease,” said Carole Ho, MD, Chief Medical Officer at Denali. “Initiation of the LUMA study marks an important milestone in the development of BIIB122 as a potentially first-in-class oral LRRK2 therapy for Parkinson’s disease. We look forward to continuing our collaboration with Biogen and the Parkinson’s community in our unified goal to develop BIIB122 as a potential treatment option for people and families living with Parkinson’s disease.”

BIIB122 is an investigational small molecule inhibitor of LRRK2 that was discovered and developed by Denali. Denali and Biogen are co-developing and co-commercializing BIIB122 for the potential treatment of Parkinson’s disease. The BIIB122 clinical development program includes both the LUMA Phase 2b study and the Phase 3 LIGHTHOUSE study in individuals with Parkinson’s disease with LRRK2 pathogenic variants.

“Inhibition of LRRK2 is a novel approach designed to target an underlying biological pathway implicated in Parkinson’s disease,” said Samantha Budd Haeberlein, PhD, Senior Vice President, Head of Neurodegeneration Development at Biogen. “Together, Biogen and Denali have designed a rigorous development program to evaluate BIIB122 in patients with and without LRRK2 mutations. With the LUMA study now underway and the LIGHTHOUSE study planned to initiate this year, we have the opportunity to advance BIIB122 for the treatment of Parkinson’s disease, a progressive neurodegenerative disease with high unmet need.”

Further information about LUMA (NCT05348785) can be accessed 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.

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.

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 is providing the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing the industry’s most diversified pipeline 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.