Full results from the phase 2b LUMA showed that investigational BIIB122/DNL151 did not slow confirmed clinical worsening in early-stage Parkinson's disease compared with placebo.
Full results from the phase 2b LUMA trial (NCT05348785) showed that the investigational LRRK2 inhibitor BIIB122/DNL151 did not slow confirmed clinical worsening in people with early-stage Parkinson's disease compared with placebo, despite evidence of substantial peripheral target engagement. Researchers presented the late-breaking data at the
“While these are not the results we hoped for, these data provide important information to the Parkinson's community,” Diana Gallagher, MD, senior vice president and head of neurodegeneration clinical development at Biogen, said in a statement when the companies first disclosed LUMA's topline results in May 2026.2
LUMA was a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial enrolling adults aged 30 to 80 years with early-stage Parkinson's disease, defined as a diagnosis within 2 years of screening and Hoehn and Yahr stage I or II in the OFF state. About 80% of participants were treatment-naive, and the remainder were on stable symptomatic therapy with a monoamine oxidase B inhibitor or levodopa for less than 1 year before screening.1
A total of 648 participants were randomized to oral BIIB122/DNL151 225 mg once daily or matching placebo for a minimum of 48 and maximum of 144 weeks, across 206 sites in 5 countries. The primary endpoint was time to confirmed worsening in the modified MDS-UPDRS combined Parts II and III score, with worsening defined as an increase of 6 points or more from baseline.1,3
BIIB122/DNL151 did not demonstrate a statistically significant benefit on the primary endpoint compared with placebo (hazard ratio, 1.04; 95% CI, 0.85-1.28; P =.4538), and did not show benefit on secondary endpoints.
Through week 48, BIIB122/DNL151 produced more than a 90% reduction in whole blood pS935 LRRK2 and about a 50% reduction in urine bis(monoacylglycero)phosphate relative to baseline, both markers of peripheral LRRK2 kinase inhibition. In a cerebrospinal fluid substudy (n=86), the drug produced a smaller, roughly 30% peak reduction in phosphorylated Rab10 at week 24, a biomarker of LRRK2 activity in the central nervous system.1
Treatment-emergent adverse events (TEAEs) and serious AEs occurred at similar rates with BIIB122/DNL151 (92.8% and 11.5%, respectively) and placebo (89.3% and 11.9%). Headache (17.1% with BIIB122/DNL151 vs 9.2% with placebo) and falls (13.1% vs 12.5%) were the most common TEAEs. TEAEs led to study drug withdrawal in 11.2% of BIIB122/DNL151-treated participants compared with 4.6% of placebo-treated participants.
BIIB122/DNL151 had originally been tested in 2 late-stage studies: LUMA, in early-stage idiopathic and LRRK2-mutation-associated Parkinson's disease, and the phase 3 LIGHTHOUSE trial, specifically in LRRK2-mutation carriers. Biogen and
Following LUMA's primary endpoint miss, Biogen and Denali said in May 2026 that they would discontinue BIIB122/DNL151 development in idiopathic Parkinson's disease. “While we are disappointed with these results, we believe the LUMA study was a robust test of LRRK2 inhibition,” said Peter Chin, MD, chief medical officer and head of development at Denali.2
Denali continues to independently run the phase 2a BEACON study of BIIB122/DNL151 in patients with LRRK2-mutation-associated Parkinson's disease, with data expected in the first half of 2027. Earlier in LUMA's conduct, a substudy had also evaluated smartphone-based typing metrics as a potential digital endpoint for future Parkinson's disease trials.2
