An In-Depth Report on the Investigational Drug PF-04634817

I. Executive Summary

PF-04634817 is an investigational small molecule developed primarily by Pfizer Inc., designed as an orally administered dual antagonist of the C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5). The therapeutic rationale underpinning its development was the critical role these chemokine receptors play in mediating inflammatory cell recruitment, a key pathological process in various chronic diseases, particularly diabetic complications such as diabetic nephropathy (DN) and diabetic macular edema (DME). Preclinical studies, notably in animal models of DN, demonstrated promising efficacy in reducing kidney inflammation, glomerulosclerosis, and improving renal function parameters.

The clinical development program for PF-04634817 encompassed several Phase 1 studies in healthy volunteers (including NCT01140672) and in subjects with renal impairment to establish its safety, tolerability, and pharmacokinetic profile. These studies indicated that PF-04634817 was generally well-tolerated, allowing progression to Phase 2 trials. Phase 2 studies subsequently evaluated the efficacy and safety of PF-04634817 in patients with DN (NCT01712061) and DME (NCT01994291).