Pivotal Trials Show Tibotec’s HIV Drug Halves Rate of Treatment Withdrawal

Studies find TMC278 to be as effective as EFV in combination therapy.

Tibotec Pharmaceuticals reported positive data from two pivotal trials comparing its non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV therapy candidate TMC278 with efavirenz (EFV) in treatment-naive adults receiving a nucleoside/nucleotide background regimen. Pooled data from the Echo and Thrive studies showed 84.3% of TMC278-treated patients achieved an undetectable viral load within 48 weeks, compared with 82.3% of the EFV-treated groups. Patients in the TMC278 cohort were also half as likely to suffer adverse events leading to treatment discontinuation. 3.4% of patients in the TMC278 group discontinued therapy due to adverse events, compared with 7.6% of those in the EFV group. Tibotec said it aims to submit the Echo and Thrive data as part of its NDA for the use of TMC278 in this patient population.

TMC278 is a a diarylpyrimidine-derivative NNRTI that the firm claims demonstrates high intrinsic activity against both wild-type HIV-1 in vitro and against HIV strains harboring resistance-inducing mutations. The drug’s long half-life allows for once-daily dosing.

Tibotec already has two anti-HIV drugs licensed in major markets; the NNRTI etravirine and the protease inhibitor darunavir. Another NNRTI, dapivirine, is being taken through Phase I/II trials by the International Partnership for Microcides (IPM), formulated into a silicone-based vaginal ring. Trials in Europe have already shown the product to be safe, IPM claims, and the first trial evaluating the vaginal ring in Africa women was initiated in June.  A Phase III program to test the ability of dapivirine rings to prevent HIV infection is scheduled to begin in Africa in 2011, with results due in 2015, the organization states.

Tibotec’s tuberculosis therapy program is focused on development of the Phase II-stage candidate, TMC207, which is partnered with the Global Alliance for TB Drug Development. Under terms of the deal signed in 2009, Tibotec retains responsibility for worldwide development and access to TMC207 for treating multidrug-resistant TB. The TB alliance has a royalty-free license covering worldwide development and access toTMC207 in the field of drug-susceptibleTB.

Tibotec is separately developing two drug candidates against genotype-1 HCV. Telaprevir (VX-950) is an oral inhibitor of hepatitis C virus protease, which is being developed in collaboration with Vertex Pharmaceuticals under a deal signed in 2006. The drug is progressing through Phase III trials. TMC435 is a selective small molecule inhibitor of the viral NS3/4A protease, which Tibotec is currently taking through Phase IIa and IIb development.