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The Phase 2b LUMA study of BIIB122 in early-stage Parkinson’s disease did not meet its primary or secondary endpoints
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Based on data from the Phase 2b LUMA study, Biogen and Denali will discontinue development of BIIB122 in idiopathic Parkinson’s disease
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Denali continues to independently conduct the Phase 2a BEACON study in carriers of a pathogenic LRRK2 variant
CAMBRIDGE, Mass. and SOUTH SAN FRANCISCO, Calif., May 21, 2026 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) and Denali Therapeutics Inc. (Nasdaq: DNLI) today announced topline results from the Phase 2b LUMA study evaluating BIIB122 (DNL151), an investigational small molecule inhibitor of LRRK2 (leucine-rich repeat kinase 2), in individuals with early-stage Parkinson’s disease. Results from the study show that BIIB122 did not slow the progression of Parkinson’s disease versus placebo, as measured by the primary endpoint of Time to Confirmed Worsening in the modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III combined score. Secondary endpoints also did not show a benefit with BIIB122. Exploratory biomarker endpoints demonstrated >90% kinase inhibition of peripheral LRRK2 (phosphoserine 935) and, in a cerebrospinal fluid (CSF) sub-study, up to approximately 30% reduction observed in a biomarker of LRRK2 activity (phosphorylated Rab10). Expected levels of BIIB122 in the blood and CSF were sustained across the study. BIIB122 was generally well tolerated with an acceptable safety profile. Based on these results, Biogen and Denali will discontinue further development of BIIB122 in idiopathic Parkinson’s disease. Denali will continue to independently conduct the Phase 2a BEACON study evaluating the small molecule inhibitor in carriers of a pathogenic LRRK2 variant.
“While these are not the results we hoped for, these data provide important information to the Parkinson’s community and will be presented at an upcoming scientific conference,” said Diana Gallagher, MD, Senior Vice President and Head of Neurodegeneration Clinical Development at Biogen. “We are profoundly grateful to the patients, families, and investigators who participated in this study and contributed to our understanding of Parkinson’s disease.”
LUMA was a Phase 2b multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of BIIB122 compared to placebo in 648 people with early-stage Parkinson’s disease between the ages of 30 and 80. Participants received BIIB122 or placebo for a minimum of 48 weeks and up to 144 weeks. The study included individuals with early-stage Parkinson’s disease with or without a pathogenic LRRK2 variant. The LUMA study was designed to evaluate the potential of LRRK2 inhibition to address the underlying biology of Parkinson’s disease.
“While we are disappointed with these results, we believe the LUMA study was a robust test of LRRK2 inhibition using BIIB122 in idiopathic Parkinson’s disease and there is more to be learned about LRRK2 as a potential therapeutic target,” said Peter Chin, M.D., Chief Medical Officer and Head of Development of Denali Therapeutics. “Independently, we continue to study this small molecule inhibitor in the Phase 2a BEACON study in individuals with Parkinson’s disease who are confirmed by genetic testing to be carriers of a pathogenic LRRK2 variant, which is associated with increased LRRK2 kinase activity. We look forward to further analysis of the LUMA data and the results from BEACON to inform next steps for development.”
The global Phase 2a BEACON study is designed to assess safety, pharmacokinetics and biomarkers of lysosomal pathway engagement, which will inform the biomarker profile in LRRK2 pathogenic variant carriers and the impact of LRRK2 inhibition. Data from the BEACON study is anticipated in the first half of 2027. The BEACON study is being operationalized by Denali and funded under a Collaboration and Development Funding Agreement between Denali and a third party.
Biogen and Denali will share detailed findings from the LUMA study at an upcoming scientific conference to contribute to the broader understanding of Parkinson’s disease and LRRK2 biology.
About Parkinson’s Disease
Parkinson’s disease is a progressive neurodegenerative disorder that affects movement and a wide range of non-motor functions. It is characterized by motor symptoms such as tremor, muscle stiffness, slowness of movement, and balance difficulty, as well as non-motor symptoms including sleep disturbances, mood changes, and cognitive impairment. One million people in the U.S. and more than 10 million people worldwide are estimated to have Parkinson’s disease. Parkinson’s disease is especially difficult to develop drugs for because of its complexity, with patients presenting differently and responding variably to treatment. The lack of reliable biomarkers, along with diverse and often unknown biological causes of the disease, also makes it challenging to track disease progression in clinical trials.
About LRRK2
Following discovery of the LRRK2 (leucine-rich repeat kinase 2) 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 LRRK2 account for 4-5% of familial and 1-2% of sporadic Parkinson’s disease.1, 2 In addition, common variants in and around LRRK2 have been identified as risk factors for sporadic Parkinson’s disease.
While the exact pathogenic mechanisms remain unknown, LRRK2 is believed to play a role in intracellular trafficking in the endolysosomal system, and the endolysosomal system is overrepresented among rare and common risk gene variants for Parkinson’s disease.3,4,5 Lysosomal dysfunction is a central pathogenic driver of Parkinson’s disease, characterized by failure of the cell’s waste disposal system (lysosomes) to break down proteins, which then accumulate and create aggregates that can cause neuronal degeneration.6
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
About Denali Therapeutics
Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier using its proprietary TransportVehicle™ platform. With a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, Denali is advancing toward its goal of delivering effective medicines to transform life for people with neurodegenerative diseases, lysosomal storage disorders and other serious diseases.
References:
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Healy DG, Falchi M, O'Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol. 2008;7(7):583-90.
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Hernandez DG, Reed X, Singleton AB. Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. J Neurochem. 2016;139 Suppl 1:59-74. Epub 2016/04/18.
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Bonet-Ponce, Luis et al. “LRRK2 mediates tubulation and vesicle sorting from lysosomes.” Science advances vol. 6,46 eabb2454. 11 Nov. 2020, doi:10.1126/sciadv.abb2454
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Robak, Laurie A et al. “Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.” Brain : a journal of neurology vol. 140,12 (2017): 3191-3203. doi:10.1093/brain/awx285
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Smolders, Stefanie, and Christine Van Broeckhoven. “Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson's disease pathogenesis.” Acta neuropathologica communications vol. 8,1 63. 6 May. 2020, doi:10.1186/s40478-020-00935-4
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Moors, Tim et al. “Lysosomal Dysfunction and α-Synuclein Aggregation in Parkinson's Disease: Diagnostic Links.” Movement disorders : official journal of the Movement Disorder Society vol. 31,6 (2016): 791-801. doi:10.1002/mds.26562