Arvinas ARV-102 Clinical Trial Shows Over 50% Reduction in LRRK2
Arvinas presented data from a Phase 1 clinical trial of ARV-102, an investigational PROteolysis TArgeting Chimera, or PROTAC, degrader designed to specifically target and degrade leucine-rich repeat kinase 2 (LRRK2). In the trial, ARV-102 demonstrated approximately 50% or greater reduction of LRRK2 in cerebrospinal fluid, or CSF, at all doses by day 14 and maintained the reduction through day 28 in patients with Parkinson's disease, or PD. The Company targeted a 50% reduction based on data showing that patients with PD have a two-fold elevation of LRRK2. The MD cohort of the Phase 1 clinical trial conducted in patients with PD evaluated ARV-102 oral doses ranging from 20 mg to 80 mg daily for 28 days. Key findings from the trial showed: ARV-102 exposure in CSF increased in a dose-dependent manner after multiple doses, indicating brain penetration; ARV-102 achieved approximately 50% or greater LRRK2 reduction in CSF at all doses by day 14 and maintained the reduction through day 28, indicating substantial central LRRK2 protein degradation; Treatment resulted in reduction of LRRK2 variant and expression-dependent endolysosomal and neuroinflammatory biomarkers previously shown to be elevated in neurodegenerative diseases like PD and progressive supranuclear palsy; and ARV-102 was generally safe and well tolerated with no serious adverse events reported after multiple doses. ARV-102 is an investigational, orally bioavailable PROTAC designed to cross the blood-brain barrier and specifically target and degrade LRRK2. The ARV-102 Phase 1 clinical trial is designed to assess the safety, pharmacokinetics, and pharmacodynamics of orally administered ARV-102 in patients with PD. Data presented are from the MD cohort of the single-center, randomized, double-blind, placebo-controlled trial. In the MD cohort, patients were randomized to either placebo or multiple oral doses of ARV-102 for 28 days with follow-up at day 42. Multiple oral doses of ARV-102 were well tolerated in participants with PD. All treatment-emergent adverse events and treatment-related adverse events were mild in severity, with no SAEs, discontinuations, or deaths reported. No significant changes in lung functions or respiratory symptoms were observed during the 28 days of treatment or during follow-up. Based on the positive outcomes of the Phase 1 clinical trial, Arvinas plans to continue investigation of ARV-102 in neurodegenerative diseases associated with LRRK2 and endolysosomal dysfunction.
