Biogen and Denali Therapeutics have reported data from the Phase IIb LUMA study evaluating their investigational leucine-rich repeat kinase 2 (LRRK2) inhibitor, BIIB122 (DNL151), for early-stage Parkinson’s disease.
The multi-centre, global, double-blind, placebo-controlled, randomised trial included 648 patients aged 30 to 80 years with early-stage Parkinson’s disease, with or without a pathogenic LRRK2 variant.
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Patients received either BIIB122 or a placebo for 48 to 144 weeks.
The primary endpoint measured by time to confirmed worsening in the combined Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III score showed that BIIB122 did not slow disease progression versus a placebo.
Secondary endpoints also did not demonstrate benefit. Exploratory biomarker analysis revealed that BIIB122 achieved an over 90% inhibition of peripheral LRRK2 kinase.
A cerebrospinal fluid sub-study also observed up to approximately 30% reduction in a biomarker of LRRK2 activity (phosphorylated Rab10).
Target levels of BIIB122 in blood and CSF were maintained throughout the trial period. The safety profile of BIIB122 was deemed acceptable, with general tolerability observed.
Given these findings, Biogen and Denali will discontinue further development of BIIB122 in idiopathic Parkinson’s disease.
Denali will continue the independent Phase IIa BEACON study, which will evaluate BIIB122 in participants carrying a pathogenic LRRK2 variant.
BEACON is focused on the assessment of safety, pharmacokinetics, and biomarkers related to lysosomal pathway engagement, specifically in pathogenic variant carriers. Results from BEACON are expected in the first half of 2027.
Biogen senior vice-president and neurodegeneration clinical development head Diana Gallagher said: “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.
“We are profoundly grateful to the patients, families, and investigators who participated in this study and contributed to our understanding of Parkinson’s disease.”
In March 2026, Biogen’s successor to Spinraza (nusinersen) showed benefit in spinal muscular atrophy (SMA) patients who had suboptimal clinical status despite prior administration of gene therapy.
