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and Hepatitis.com Coverage of the
XVIII International AIDS Conference (AIDS 2010) July 18 - 23, 2010, Vienna, Austria
New NNRTI Rilpivirine (TMC278) Shows Potent Antiviral Activity and Good Tolerability in Phase 3 Trials, FDA Application Submitted
Rilpivirine is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that appears to have a long half-life in the body (about 45 hours) and a somewhat different resistance profile than existing drugs in its class.
In prior Phase 2b studies, rilpivirine demonstrated sustained efficacy similar to that of efavirenz (Sustiva), but with generally better tolerability. A low dose of 25 mg once-daily was chose for further testing.
Cal Cohen from the Community Research Initiative of New England presented data from a pooled 48-week primary analysis of combined data from 2 Phase 3 trials, ECHO (TMC278-C209) and THRIVE (TMC278-C215). The studies are scheduled to continue through 96 weeks.
These international trials together enrolled a total of 1368 previously untreated HIV positive adults. About 75% were men, the median age was 36 years, about 60% were white, about 25% were black, and just over 10% were Asian; about 8% had hepatitis B or C coinfection.
At baseline, the median viral load was 100,000 copies/mL and the median CD4 cell count was about 250 cells/mm3. Participants had no known NNRTI resistance-associated mutations (which can exist due to transmission of resistant virus even in people with no prior antiretroviral drug exposure).
In ECHO, 690 participants were randomly assigned to receive 25 mg once-daily rilpivirine or 600 mg once-daily efavirenz (Sustiva), both in combination with tenofovir/emtricitabine (the drugs in Truvada).
In THRIVE, 678 patients were again randomly assigned to the same doses of rilpivirine or efavirenz, but here they could also take tenofovir/emtricitabine (60%), zidovudine/lamivudine (Combivir)(30%), or abacavir/lamivudine (Epzicom)(10%).
main objective was to demonstrate whether rilpivirine is non-inferior
to efavirenz in suppressing HIV viral load using an intent-to-treat
"TLOVR" analysis, within a margin of 12%.
Based on these findings, investigators concluded, "TMC278 [rilpivirine] was efficacious and well tolerated in a large and diverse group of treatment-naive patients."
They characterized response rates as being "among the highest observed in recent treatment-naive trials."
On July 27, Tibotec Pharmaceuticals announced that it has submitted a New Drug Application (NDA) to FDA, based on the 48-week data from ECHO and THRIVE. Regulatory submissions for rilpivirine in other countries are expected in coming months, the company said.
Tibotec also confirmed that it has entered into a license and collaboration agreement with Gilead Sciences to develop a once-daily fixed-dose pill containing rilpivirine plus Gilead's 300 mg tenofovir/200 mg emtricitabine combination. If approved, this would create a single-tablet regimen to compete with Atripla (tenofovir/emtricitabine/efavirenz).
Community Research Initiative of New England, Boston, MA; Saint-Louis Hospital and University of Paris, Department of Infectious Diseases, Paris, France; Hospital Juan A Fernández and Fundación Huesped, Buenos Aires, Argentina; Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Barcelona, Spain; Dr J Fourie Medical Centre, KwaZulu Natal, South Africa; Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil; Beijing You'an Hospital, Beijing, China; Royal Free Hospital, London, UK; University of Alabama at Birmingham, Infectious Diseases, Birmingham, AL; Chiang Mai University, Section of Infectious Disease, Chiang Mai, Thailand; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc, Titusville, NJ.