An In-Depth Analysis of Cenicriviroc (DB11758): A Dual CCR2/CCR5 Antagonist

Executive Summary

Cenicriviroc is an investigational, orally bioavailable small molecule drug candidate characterized by a unique pharmacological profile as a dual antagonist of the C-C chemokine receptors type 2 (CCR2) and type 5 (CCR5).[1] This dual mechanism of action provided a strong rationale for its development across two distinct and significant therapeutic areas: as an antiretroviral agent for the treatment of Human Immunodeficiency Virus (HIV) infection and as a novel anti-inflammatory and antifibrotic therapy for Nonalcoholic Steatohepatitis (NASH).[3]

The clinical development of Cenicriviroc yielded a complex and ultimately cautionary narrative. In the context of HIV, a Phase 2b clinical trial demonstrated that Cenicriviroc, as part of a combination regimen, had comparable virologic efficacy to the standard-of-care agent efavirenz. It also offered significant ancillary benefits, including a more favorable lipid profile and a reduction in systemic inflammation markers. However, development for this indication was not advanced to Phase 3.[4]

The primary focus of its later-stage development shifted to NASH, a field with a substantial unmet medical need. The Phase 2b CENTAUR study produced a dichotomous result: while it failed to meet its primary endpoint related to the resolution of steatohepatitis, it achieved a statistically significant secondary endpoint, demonstrating a notable improvement in liver fibrosis.[6] This promising antifibrotic signal prompted the initiation of the large-scale Phase 3 AURORA trial.