The companies announced on Thursday that the global LUMA study failed to meet its primary endpoint, with BIIB122 showing no significant benefit compared with placebo in slowing progression of early-stage Parkinson’s disease.
The study enrolled 648 patients aged 30-80 and evaluated the small molecule inhibitor during treatment periods ranging from 48 to 144 weeks.
BIIB122 is designed to inhibit leucine-rich repeat kinase 2 (LRRK2), an enzyme associated with one of the most common genetic drivers of Parkinson's disease.
Mutations in the LRRK2 gene are linked to impaired cellular waste-disposal pathways and toxic protein accumulation that contribute to neuronal degeneration.
According to the companies, the therapy did not delay worsening symptoms as measured by the modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III combined score.
Secondary endpoints also failed to demonstrate clinical benefit.
However, exploratory biomarker analyses suggested the drug achieved the intended biological activity. Biogen reported more than 90% inhibition of peripheral LRRK2 kinase activity and reductions in cerebrospinal fluid biomarkers linked to LRRK2 signalling.
The treatment was also generally well tolerated and maintained expected drug exposure levels in blood and cerebrospinal fluid throughout the study.
Diana Gallagher, Senior Vice President and Head of Neurodegeneration Clinical Development at Biogen, said the findings would still contribute valuable insight into Parkinson’s biology and future therapeutic development.
We are profoundly grateful to the patients, families and investigators who participated in this study and contributed to our understanding of Parkinson’s disease.
Despite the setback, Denali will continue independently with the Phase IIa BEACON study, which is evaluating BIIB122 specifically in Parkinson’s patients carrying pathogenic LRRK2 variants identified through genetic testing.
The company believes this genetically defined subgroup may provide further insight into whether targeted LRRK2 inhibition could still offer therapeutic potential.
The BEACON study is expected to generate data in the first half of 2027.
The result marks another challenge for the Parkinson’s disease drug development landscape, where translating promising biomarker activity into measurable clinical benefit continues to prove difficult.
Biogen and Denali said in the release that detailed findings from the LUMA trial will be presented at an upcoming scientific conference.