Arvinas presented positive Phase 1 clinical trial data for ARV-102, a PROTAC degrader targeting LRRK2, a protein implicated in Parkinson’s disease and progressive supranuclear palsy. The data, presented at the 2025 AD/PD™ conference, showed ARV-102 was well-tolerated, reached the brain, and significantly reduced LRRK2 levels in both the central nervous system and peripheral blood. Based on these findings, a Phase 1 trial in Parkinson’s disease patients has begun.
This development is important because it validates the potential of PROTAC degraders to target previously “undruggable” proteins like LRRK2, opening up new therapeutic avenues for neurodegenerative diseases. The successful brain penetration of ARV-102 is particularly crucial, as many drugs struggle to cross the blood-brain barrier, hindering their effectiveness in treating neurological conditions. This success could encourage further investment and research in PROTAC-based therapies for other brain diseases.
The Phase 1 trial in healthy volunteers showed that ARV-102 was safe and well-tolerated at doses up to 200mg (single dose) and 80mg (multiple doses). Significant LRRK2 reduction (over 50% in cerebrospinal fluid and over 90% in peripheral blood) was achieved at doses of 60mg or higher (single dose) and 20mg or higher (multiple daily doses). The drug also exhibited a favorable pharmacokinetic profile with a half-life of 73 hours. Downstream markers of LRRK2 activity were also impacted, suggesting the drug engaged its target and affected the relevant biological pathways.
The positive Phase 1 data and the initiation of a Parkinson’s disease patient trial mark significant progress for Arvinas and the field of targeted protein degradation. The continued clinical development of ARV-102 will be closely watched, as it could potentially lead to a new treatment option for patients with Parkinson’s disease and other LRRK2-related disorders. Positive results from the ongoing Parkinson’s disease trial could significantly impact Arvinas’ position within the neurodegenerative disease treatment landscape.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
