Biogen and Denali’s Parkinson’s disease drug failed to significantly slow disease progression in a Phase 2b study, missing both primary and secondary endpoints.
Biogen and Denali Therapeutics’ investigational Parkinson’s disease drug failed to significantly slow disease progression in a Phase 2b study, prompting the partners to abandon the asset.
The Phase 2b LUMA trial enrolled nearly 650 patients with early-stage Parkinson’s disease who were then randomly given either the investigational drug, called BIIB122, or placebo. Without revealing specific data, the companies on Thursday said that their asset did not significantly slow disease progression versus placebo.
BIIB122, also called DNL151, is an orally available small-molecule blocker of LRRK2, a protein commonly found in the brain that helps form the structure of the cell. LRKK2 also participates in signal transduction and other enzymatic functions. LRRK2 dysfunction has been linked to Parkinson’s.
BIIB122 also missed key secondary endpoints, including disability and impairments in activities of daily living. Biogen and Denali will no longer invest in BIIB122’s development for idiopathic Parkinson’s, according to their news release.
“We always viewed this readout as higher-risk,” analysts at Stifel told investors in a note on Thursday evening. “The mechanistic rationale of LRRK2 inhibition in carriers is strong, but the rationale in idiopathic [Parkinson’s] is more speculative,” the analysts explained.
The change of course came five years after early data showed that BIIB122 led to “robust reductions” in disease biomarkers, including those that are downstream the LRRK2 signaling cascade. Aside from LUMA, Denali also launched the Phase 2a BEACON trial to evaluate BIIB122 specifically for the treatment of patients with LRRK2-associated Parkinson’s. BEACON isn’t being run in partnership with Biogen.
Denali intends to push through with BEACON despite LUMA’s failure, according to the Thursday announcement. Stifel appears to be more optimistic about BEACON. “We do think this is conceptually more interesting,” the analysts wrote, pointing to “evidence of target engagement” in LUMA.
Indeed, Biogen and Denali reported that BIIB122 treatment elicited more than 90% inhibition of LRRK2 outside the central nervous system and around 30% inhibition in the cerebrospinal fluid.
Even if BEACON succeeds, however, it remains unclear to Stifel what that might mean for Denali’s business. “There are other questions here on the size and viability of the commercial opportunity,” the analysts said, noting that LRRK2 is present in only 1% to 2% of Parkinson’s patients. Data from BEACON are expected in the first half of 2027.
