Tobira Therapeutics, Inc. presented positive results from the Phase 2b clinical trial (Study 202) of cenicriviroc (CVC) at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013). CVC is a novel, oral, once-daily, dual CCR5/CCR2 inhibitor in clinical development for the treatment of HIV infection. Study 202 is a randomized, double-blind, double-dummy, dose-finding, controlled study that enrolled 143 HIV-1 infected patients with CCR5-tropic HIV infection. At week 24, 100mg or 200mg of once-daily CVC plus Truvada(R) (emtricitabine/tenofovir disoproxil fumarate) demonstrated similar virologic success rates (76% and 73%) compared to once-daily Sustiva(R) (efavirenz or EFV) plus Truvada (71%). A favorable safety and tolerability profile was observed in CVC-treated patients. In addition, a significant decrease in monocyte activation, measured by reduction in sCD14 levels, was seen in CVC-treated patients. The complete week 24 results from Study 202 were presented as a Late Breaker Abstract Presentation by Joseph C. Gathe, MD during the session titled ‘New Agents and New Insights’ in a talk titled ‘Week 24 Primary Analysis of Cenicriviroc vs Efavirenz, in Combination with FTC/TDF, in Treatment-naïve HIV-1 Infected Adults with CCR5-tropic Virus,’ (Abstract 106LB). Study 202 Result Highlights: At the primary endpoint of 24 weeks, the percentage of patients in the 100mg and 200mg CVC study arms achieving virologic success, defined as HIV viral load< 50 copies/mL, was 76% and 73%, respectively compared to 71% in the EFV arm. Cenicriviroc was well tolerated and lower rates of adverse events were observed in the CVC arms when compared to the EFV arm. LDL cholesterol levels decreased among patients receiving CVC, while both LDL and HDL cholesterol levels increased among patients receiving EFV. Anti-inflammatory markers correlating to the CCR2 ligand (MCP-1) increased in a dose-dependent manner among patients who received CVC. Finally, levels of sCD14, a marker of monocyte activation and an independent predictor of mortality in HIV infection, decreased over the course of the study for CVC-treated subjects, but increased for EFV-treated subjects. Study 202 Design: Study 202 is a double-blind, double-dummy, randomized, controlled Phase 2b trial, evaluating once-daily doses of CVC 100mg or 200mg compared to once-daily Sustiva(R) (efavirenz), each in combination with open-label Truvada(R) (emtricitabine/tenofovir disoproxil fumarate). The study enrolled a total of 143 treatment-naïve, HIV-1 infected adults with CCR5-tropic virus. Patients with CCR5-tropic virus represent approximately 80% of the treatment-naïve HIV-infected population. The primary objective of this trial is to determine the efficacy and safety of CVC when compared to efavirenz, both as part of combination HIV therapy. Additionally, the trial assesses changes in biomarkers associated with inflammation, metabolic parameters, and immune function. The study will continue for a total duration of 48 weeks for further evaluation of efficacy and safety. Phase 3 Development Strategy: Based on the results of Study 202, Tobira is preparing for CVC's Phase 3 registrational program. Tobira plans to conduct two, randomized, controlled, double-blinded, double-dummy, Phase 3 trials, each in approximately 750 HIV-1 infected adults with CCR5-tropic HIV virus. These trials will evaluate efficacy and safety of CVC-containing combination regimens compared to treatment guideline-preferred first-line treatment options. The trials will be designed with a 48-week primary analysis to support global regulatory filings, and will continue for 96-weeks in the final analysis. The trials will also assess the effect of CVC on inflammatory and metabolic comorbidities often associated with chronic HIV-1 infection. Patients with HIV infection, even those well-controlled on antiretroviral therapy, experience these diseases earlier and at higher rates than uninfected individuals.

Tobira Therapeutics, Inc. announced positive results from the 24-week primary analysis of Study 202, the Phase 2b study of cenicriviroc (CVC). CVC is a novel, oral, once-daily, dual CCR5/CCR2 inhibitor. Tobira is investigating CVC for the treatment of HIV-1 infected adults with CCR5-tropic virus. This 143-patient, double-blind, double-dummy, randomized, controlled Phase 2b trial (Study 202, NCT01338883) met its primary objective over 24 weeks of treatment. A similar proportion of patients treated with either 100mg or 200mg of once-daily CVC plus Truvada(R) (emtricitabine/tenofovir disoproxil fumarate) achieved undetectable HIV viral load (<50c/mL) at week 24 when compared to patients treated with once-daily Sustiva(R) (efavirenz) plus Truvada(R) . A favorable safety and tolerability profile was observed in CVC-treated patients. The study enrolled a total of 143 treatment-na ve, HIV-1 infected adults with CCR5-tropic virus. Patients with CCR5-tropic virus represent approximately 80% of the treatment-na ve HIV-infected population. The primary objective of this trial is to determine the efficacy and safety of CVC when compared to efavirenz, both as part of combination HIV therapy. Additionally, the trial assesses changes in biomarkers associated with inflammation, metabolic parameters, and immune function.

Tobira Therapeutics, Inc. Presents at 31st Annual JPMorgan Healthcare Conference, Jan-07-2013 09:30 AM. Venue: Westin St. Francis Hotel, San Francisco, California, United States. Speakers: Andrew Hindman, Chief Executive Officer, President and Director.