LRRK2 inhibitor failure pushes Parkinson’s field toward genetic enrichment

For years, researchers hoped that LRRK2 — a target rooted in Parkinson’s genetics — might benefit patients broadly, even those without the underlying genetic variants. A Phase IIb miss by Biogen and Denali is making that case harder to sustain, although some still believe idiopathic patients can be reached via LRRK2.

In May, Biogen Inc. (NASDAQ:BIIB) and Denali Therapeutics Inc. (NASDAQ:DNLI) announced LRRK2 inhibitor BIIB122 (DNL151) failed to slow disease progression in the Phase IIb LUMA study, which enrolled early Parkinson’s patients regardless of LRRK2 variant status. The companies discontinued the drug in idiopathic Parkinson’s, and Denali is independently testing it in a smaller trial limited to confirmed variant carriers...