SAN FRANCISCO, Feb. 17 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).
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"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."
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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."
About the trial
Study 652-2-201 was a double-blind, placebo-controlled, dose-escalation trial in which patients were randomized to receive once-daily TBR-652 in the following dosing cohorts: 25 mg (n=8), 50 mg (n=8), 75 mg (n=9), 100 mg (n=10), and 150 mg (n=9); 10 patients were randomly assigned to receive placebo. All patients were HIV treatment-experienced, though none had previously been treated with a CCR5 antagonist.
TBR-652 monotherapy produced dose-dependent declines in HIV RNA with a median nadir decline from baseline in HIV viral load of up to 1.8 log10 copies/mL. In addition, dose-dependent changes in MCP-1 concentrations were also observed, demonstrating TBR-652's dual CCR5/CCR2 mechanism of action and potential anti-inflammatory benefits. Most adverse events in the study were mild in severity (Grade 1). There were no clinically significant trends in adverse events, laboratory tests, vital signs or electrocardiogram measurements. Additionally, there were no liver function test elevations of Grade 1 or greater.
About Tobira Therapeutics, Inc.
Tobira Therapeutics is a private biopharmaceutical company which is focused on developing and commercializing innovative antiviral compounds to treat HIV disease. The company was founded in 2006 by Eckard Weber, M.D., a partner at the venture capital firm Domain Associates, to develop novel treatments for HIV disease. Tobira has assembled a highly experienced management team with decades of clinical and commercial development experience specifically in HIV/AIDS drug development.
www.tobiratherapeutics.com
SOURCE Tobira Therapeutics, Inc.
