PK/PD data demonstrates clear relationship between TBR-652 plasma concentrations and antiviral activity

Pharmacokinetic/pharmacodynamic (PK/PD) data for TBR-652, which is being developed by Tobira Therapeutics for the treatment of HIV infection, show a strong relationship between drug exposure and viral suppression with this next-generation CCR5 receptor antagonist. These data were presented here today at the 17th Conference on Retroviruses and Opportunistic Infections (CROI).

"These data demonstrate a clear and consistent relationship between TBR-652 plasma concentrations and antiviral activity," said David Martin, PharmD, Tobira Therapeutics, lead author of the PK/PD study. "TBR-652's potent, dose-dependent decreases in viral load, obtained without the need for a ritonavir-boost, illustrate the potential for this compound in fixed-dose antiretroviral drug combinations for the treatment of HIV disease."

In a Phase IIa trial involving 54 treatment-experienced HIV infected patients, a 10-day course of once-daily, TBR-652 monotherapy produced a median nadir decline from baseline in HIV viral load of up to 1.8 log10 copies/mL (Abstract 53, CROI 2010). Using a simple inhibitory Emax model, steady state plasma concentrations of TBR-652 were highly correlated with reductions from baseline in HIV RNA levels. The PK/PD model estimated a maximal antiviral effect (Emax) for TBR-652 of ~ 1.5 log10 copies/mL.  The plasma concentrations of TBR-652 associated with this Emax were easily achieved at doses of greater than or equal to 75 mg/day.  Investigators also observed significant viral load suppression persisting throughout the study's 30-day observation period.

"These PK/PD data for TBR-652 align with previously presented results and support the ongoing development of this exciting compound," said James Sapirstein, President and CEO of Tobira Therapeutics. "These latest data further differentiate TBR-652 from other CCR5 antagonists and provide insights into the future path forward for this drug."