Arvinas’ ARV-102 Delivers >50% CSF LRRK2 Degradation and Biomarker Reductions
Arvinas’ ARV-102 achieved ≥50% LRRK2 reduction in CSF by day 14, maintained through day 28 across 20–80 mg once-daily doses in Parkinson’s patients and reduced endolysosomal biomarkers CD68 and GPNMB. The oral PROTAC was well tolerated with no serious adverse events, supporting a Phase 1b PSP trial in Q2 2026.
1. Phase 1 Trial Design
The single-center, randomized, double-blind, placebo-controlled multiple-dose cohort evaluated ARV-102 in Parkinson’s patients receiving 20 mg, 40 mg or 80 mg once daily for 28 days. Participants underwent CSF sampling at baseline, day 14, day 28 and follow-up at day 42 to assess pharmacokinetics and pharmacodynamics.
2. LRRK2 Degradation Results
ARV-102 achieved ≥50% reduction of LRRK2 in cerebrospinal fluid by day 14 at all dose levels and maintained this reduction through day 28. CSF exposure increased in a dose-dependent manner, confirming brain penetration and substantial central target engagement.
3. Biomarker and Safety Profile
Treatment reduced neuroinflammatory and endolysosomal biomarkers such as CD68 and GPNMB, which are elevated in Parkinson’s and PSP. All adverse events were mild, with no serious adverse events, discontinuations or respiratory changes reported over the 28-day dosing period.
4. Next Steps and PSP Development
Based on these data, development will expand into progressive supranuclear palsy with a Phase 1b trial planned for Q2 2026 and potential registrational study initiation in late 2026. Parallel evaluation of ARV-102 in Parkinson’s disease continues under regulatory review.