October 6, 2026

@michaelokun

Long anticipated results are out for the Phase 2b LUMA trial that tested BIIB122/DNL151, an oral brain-penetrant inhibitor of LRRK2, as a potential disease-modifying therapy in 648 participants with early-stage Parkinson’s disease. Results just announced in a late breaking abstract at the MDS Congress in Seoul this week. Despite clear evidence that the drug engaged its biological target, including >90% reduction in blood pS935 LRRK2, ~50% reduction in urinary BMP and ~30% peak reduction in CSF pRAB10; this biological activity did not translate into clinical benefit. BIIB122/DNL151 did not significantly delay worsening on the combined MDS-UPDRS Parts II and III primary endpoint and showed no benefit on secondary outcomes. Overall adverse and serious adverse event rates were similar to placebo, although treatment discontinuation due to adverse events was higher with BIIB122/DNL151. This is an important and sobering result: the drug appears to have hit the LRRK2 pathway, but hitting the biological target was not enough to slow clinical Parkinson’s progression in this population over the period the drug was administered. https://www.mdscongress.org/Abstracts/Late-breaking