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A first-in-human trial of Arvinas’ investigational Parkinson’s’ disease therapy, ARV-102, has been able to demonstrate a drop in the multifunctional protein that has been associated with the disease whilst also surpassing the blood-brain barrier.
The Phase I single ascending dose (SAD) and multiple ascending dose (MAD) trial (EUCT-2023-507910-28-00) found ARV-102, a proteolysis targeting chimaera (PROTAC) therapy, led to a drop in leucine-rich repeat kinase 2 (LRRK2) across healthy volunteers. LRRK2 is associated with an increased risk of both autosomal dominant Parkinson’s disease and Crohn’s disease.
In the SAD cohort, a single oral dose of at least 60mg of ARV-102, alongside further once daily repeated oral doses of at least 20mg, achieved greater than 50% LRRK2 reduction in the volunteer’s cerebral spinal fluid. As well as a more than 90% LRRK2 reduction in the peripheral blood mononuclear cells (PBMCs). Investigation in the MAD cohort is still ongoing.
Additional results from the SAD cohort found that ARV-102 at single doses of more than 30mg induced more than 50% decrease in peripheral phosphor-Rab10, a biomarker used to determine the therapy’s ability to impact downstream of the blood-brain barrier.
Noah Berkowitz, CMO at Arvinas, said: “The ability of ARV-102 to cross the blood-brain barrier and degrade the LRRK2 protein offers a potentially transformative therapeutic approach in the treatment of devastating neurodegenerative diseases.
“We believe these results support continuing our ARV-102 clinical program and building upon our body of evidence for this lead PROTAC degrader candidate in our neuroscience pipeline.”
Results from the randomised, double-blind, placebo-controlled were initially announced as part of the 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) in Vienna, Austria.
In the Phase I trial, the therapy was relatively well tolerated, with some adverse events (AEs) reported. Approximately 47 volunteers were recruited across all SAD dose levels with headaches reported in 17.1% of patients. Procedural pain associated with the lumbar puncture occurred in 28.6% of treated volunteers compared to 41.7% in placebo controls.
Renewed hope for PROTAC
This comes weeks after Arvinas’ stock took a 51% after its PROTAC therapy for human epidermal growth factor receptor 2 (HER2) negative breast cancer therapy, being developed with pharma giant Pfizer, saw mixed results as it was only able to extend progression-free survival (PFS) in certain patients. The trial was conducted as part of a $2.4bn partnership between the companies. This latest Parkinson’s data gives renewed hope to Arvinas for PROTAC therapies.