TBR-652: early results for CCR5 inhibitor

26 August 2010. Related: Conference reports, Antiretrovirals, World AIDS 18 Vienna 2010.

Simon Collins, HIVi-Base

David Martin from Tobira therapeutics presented results for TBR-652, a CCR5 inhibitor with CCR2 activity. CCR2 is associated with and studied inassociation with diseases related to immune activation.

In this 10-day dose-ranging monotherapy study, 54 treatment-experienced but CCR5-naive patients were randomised to 25, 50, 75, 100, or 150 mg TBR-652, all once-daily, or to a placebo group. Inflammatory markers (MCP-1, hsCRP and IL-6) were measured at day 1 and 10.

Baseline median viral load was 4.5 log (range 3.1–6.0), approximately 30,000 copies/mL, but this presumably limited the ability to detect maximum changes for patents starting with low vireamia.

At day 10 viral load reductions of 1.4–1.8 log were seen in the 50–150 mg groups. Side effects were generally mild but were dose-related, and were higher in the 100 mg and 150 mg groups.

Although MCP-1 increased in all groups except placebo (significantly compared to placebo in the 50, 100 and 150 mg groups) this was markedly higher for the 150 mg arm (by approximately 350 pg/mL).

Phase 2b studies of the compound are expected to start early in 2011.

Reference:

Martin DE et al. TBR-652, a potent dual chemokine receptor 5/chemokine receptor 2 (CCR5/CCR2) antagonist in phase 2 development for treatment of HIVinfection. 18th IAS Conference, 18–23 July 2010, Vienna. Oral abstract MOAB0104. http://pag.aids2010.org/Abstracts.aspx?SID=631&AID=8023