CAMBRIDGE, Massachusetts and SOUTH SAN FRANCISCO, California, May 21, 2026
Biogen Inc. and Denali Therapeutics Inc. announced that the Phase 2b LUMA clinical study evaluating BIIB122 (DNL151) in patients with early-stage Parkinson’s disease failed to meet both its primary and secondary endpoints, prompting the companies to discontinue development of the investigational therapy for idiopathic Parkinson’s disease. The study tested BIIB122, a small molecule inhibitor targeting LRRK2 (leucine-rich repeat kinase 2), a genetic and biological pathway strongly linked to Parkinson’s disease progression.
Despite demonstrating strong biological target engagement, including greater than 90% inhibition of peripheral LRRK2 kinase activity and reductions in cerebrospinal fluid biomarkers associated with LRRK2 signaling, the therapy did not show meaningful clinical benefit compared with placebo in slowing disease progression. The results mark a significant setback for one of the industry’s most closely watched neurodegenerative disease programs focused on precision-targeted Parkinson’s therapies.
Phase 2b LUMA Trial Failed to Slow Parkinson’s Progression
The global Phase 2b LUMA study enrolled 648 patients with early-stage Parkinson’s disease between the ages of 30 and 80 in a randomized, double-blind, placebo-controlled trial. Participants received BIIB122 or placebo for a treatment duration ranging from 48 weeks to 144 weeks. The primary endpoint measured the time to confirmed worsening using the modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III combined score, a widely used clinical assessment tool for Parkinson’s progression.
According to topline results, BIIB122 failed to demonstrate improvement over placebo on the primary endpoint, while secondary efficacy endpoints also showed no significant benefit. However, the study confirmed that the drug successfully reached its intended biological targets, with sustained blood and cerebrospinal fluid exposure levels throughout treatment and measurable suppression of LRRK2 kinase activity. Safety findings remained generally favorable, with BIIB122 reported as well tolerated and maintaining an acceptable safety profile during the study. The companies emphasized that although the clinical outcome was disappointing, the dataset provides important scientific insights into Parkinson’s disease biology and the role of LRRK2 inhibition.
Advertisement
Companies Shift Focus Toward Genetic LRRK2 Parkinson’s Population
While development in idiopathic Parkinson’s disease will now end, Denali Therapeutics plans to continue independently advancing the ongoing Phase 2a BEACON study, which specifically targets patients carrying a pathogenic LRRK2 genetic variant associated with elevated kinase activity. Unlike the broader Parkinson’s population included in LUMA, the BEACON study focuses on genetically defined patients who may respond differently to targeted LRRK2 inhibition. The study is evaluating biomarkers, pharmacokinetics, and lysosomal pathway engagement to better understand whether precision medicine approaches could still validate LRRK2 as a therapeutic target in select patient populations.
Initial BEACON data is expected during the first half of 2027. Executives from both companies noted that Parkinson’s disease remains one of the most difficult neurodegenerative disorders for drug development due to its complex biology, variable patient responses, lack of reliable biomarkers, and diverse underlying disease mechanisms. Despite the LUMA setback, both companies stated they remain committed to contributing scientific knowledge to the broader Parkinson’s research field and plan to present detailed findings from the study at a future scientific conference.
LRRK2 Remains a Key but Challenging Drug Target
LRRK2 has been widely studied as a potential disease-modifying target in Parkinson’s disease following discoveries linking inherited LRRK2 mutations to familial Parkinson’s cases and identifying common variants associated with sporadic disease risk. Researchers believe the pathway plays a central role in the endolysosomal system, which regulates intracellular waste disposal and protein clearance in neurons. Dysfunction within this pathway is thought to contribute to the toxic protein accumulation and neuronal degeneration observed in Parkinson’s disease.
Although BIIB122 did not produce clinical benefit in the broad early-stage Parkinson’s population studied in LUMA, the strong biomarker engagement observed suggests the biology of LRRK2 may still hold therapeutic relevance in genetically selected patient groups. The outcome also underscores the growing challenge facing neurodegenerative drug developers as companies increasingly pursue precision medicine approaches to identify patient populations most likely to respond to targeted therapies.
Source: Biogen press release
