The return of PRO 140, a CCR5-directed mAb.

Abstract

Although antiretroviral therapy has become more potent and tolerable, adherence remains a barrier to continuous viral suppression and new approaches are needed. PRO 140 is a C-C chemokine receptor 5 (CCR5)-directed mAb with potential for weekly subcutaneous dosing. This review discusses data from the PRO 140 clinical development program including emerging data from ongoing efficacy studies. Phase II development of PRO 140 began over a decade ago, and recently initiated phase IIb and III trials are ongoing in study participants with virologic failure and as monotherapy maintenance in virologically suppressed study participants. PRO 140 previously demonstrated potency against CCR5-tropic virus in parenteral formulations with excellent short-term safety and tolerability, and low potential for tropism shifts or resistance. Studies are ongoing in treatment-experienced patients with multidrug resistant virus and as monotherapy maintenance in virologically suppressed patients. Partial data are available from these studies. To date, only a small number of study participants have achieved durable success on monotherapy maintenance. PRO 140 has demonstrated antiviral potency, a high barrier to resistance, and a promising short-term safety profile. Ongoing trials are exploring efficacy against CCR5-tropic virus resistant to current antiretroviral therapy and safety and efficacy as monotherapy maintenance in individuals with viral suppression.