Shares of Denali Therapeutics Inc (NASDAQ:DNLI) fell 2.9% in premarket trade Friday, while partner Biogen Inc (NASDAQ:BIIB) declined about 1% after the companies said their experimental Parkinson’s disease therapy did not succeed in a late-stage study.
The Phase 2b LUMA trial of BIIB122 (also known as DNL151), an investigational inhibitor of the LRRK2 enzyme, failed to reach both its primary and secondary endpoints in people with early-stage Parkinson’s disease. The therapy did not slow disease progression when compared with placebo, using the combined score of the modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part II and III as the measure of clinical effect.
Following the LUMA results, Biogen and Denali announced they will stop pursuing further development of BIIB122 for idiopathic Parkinson’s disease. Denali said it will continue to run the Phase 2a BEACON study independently in individuals who carry a pathogenic LRRK2 variant, with data from that study anticipated in the first half of 2027.
The LUMA trial enrolled 648 people with early-stage Parkinson’s disease between the ages of 30 and 80. Participants received either BIIB122 or placebo for a minimum duration of 48 weeks and as long as 144 weeks. While the compound produced clear biological activity - greater than 90% inhibition of peripheral LRRK2 kinase and roughly a 30% reduction in a cerebrospinal fluid biomarker of LRRK2 activity - these pharmacodynamic effects did not translate into a measurable clinical benefit on the trial’s endpoints.
BIIB122 was generally well tolerated in the study and showed an acceptable safety profile, according to the companies. The findings mean the program will not advance in idiopathic Parkinson’s disease, although one targeted genetic subgroup study will continue under Denali’s direction.
LRRK2 mutations are a recognized contributor to Parkinson’s disease in certain populations, accounting for 4% to 5% of familial cases and about 1% to 2% of sporadic cases. Biogen and Denali plan to present more detailed data from the LUMA study at an upcoming scientific conference.
Parkinson’s disease affects about one million people in the United States and more than ten million globally. The progressive neurodegenerative disorder is marked by motor symptoms such as tremor, muscle rigidity, and slowness of movement, along with non-motor features including sleep disturbances and cognitive impairment.