A New NNRTI



Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have become important components of HAART due to their high potency and convenience. Given the relatively small number of approved NNRTIs and their clinical benefits, novel NNRTIs with improved tolerability, convenience and binding to HIV-1 reverse transcriptase are needed.



Multi-disciplinary discovery research has yielded TMC278, a new NNRTI (a diarylpyrimidine (DAPY) derivative), which shows high intrinsic activity against both wild-type HIV-1 in vitro and against HIV strains harboring resistance inducing mutations. It is well tolerated, has a long half-life and allows once-daily dosing.





TMC278 Clinical Trials



An international 96-week phase IIb randomized, partially blinded dose-finding study, TMC278-C204, in treatment-naive, HIV-1 infected patients is ongoing in treatment-naive, HIV-1 infected patients. The treatment duration is being extended to 240 weeks.



In this study, seventy-six percent of patients receiving the 25 mg dose of TMC278, which is being studied in phase III trials, achieved an undetectable viral load (<50 HIV-1 RNA copies/mL) at week 96 compared with 71 percent of patients receiving efavirenz (EFV). Of patients receiving the 75 mg and 150 mg doses of TMC278, 72 percent and 71 percent achieved an undetectable viral load, respectively.



These findings were presented at the International AIDS Conference (AIDS 2008) in Mexico City.



In early 2009, the phase III clinical program completed recruitment of HIV-1 infected individuals who have not previously received antiretroviral treatment. The two pivotal double-blind studies, TMC278-C209 (ECHO) and TMC278- C215 (THRIVE) compare 25 mg once daily TMC278 against 600 mg once daily efavirenz in combination with two NRTIs. After 48 weeks of treatment, analysis of the two studies has shown that both met their primary objective of non-inferiority to efavirenz. For more information, please visit www.clinicaltrials.gov (ECHO, THRIVE).



In July 2009, a collaboration agreement was announced between Tibotec and Gilead Sciences to develop a fixed dose combination (FDC) formulation containing TMC278 and Truvada (tenofovir disoproxil fumarate and emtricitabine). In April 2010, Gilead announced that it had completed the formulation work, bringing TMC278 one step closer to become part of a 'one pill once daily' regimen.