Rilpivirine Shows Potent Activity
Rilpivirine (TMC278), an investigational next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) being developed by Tibotec, continued to show potent antiviral activity and good tolerability in previously untreated patients at 48 weeks, according to a pair of Phase III clinical trials presented at a late-breaker session at AIDS 2010 (abstract THLBB206).
Cal Cohen from the Community Research Initiative of New England reported pooled data from the ECHO (TMC278-C209) and THRIVE (TMC278-C215) trials. Together, these two multinational studies enrolled 1,368 treatment-naive participants. About 75% were men, 60% were white, and the median age was 36 years. The median CD4 cell count was about 250 cells/mm3 and patients had no known NNRTI resistance-associated mutations.
In ECHO, 690 people were randomly assigned to receive 25 mg once-daily rilpivirine or 600 mg once-daily efavirenz (Sustiva) in combination with tenofovir/emtricitabine. In THRIVE, 678 participants were randomly assigned to the same doses of rilpivirine or efavirenz, but had a choice of NRTI backbones; 60% used tenofovir/emtricitabine; 30% used zidovudine/lamivudine (Combivir), and 10% used abacavir/lamivudine (Epzicom).
People taking rilpivirine and efavirenz were equally likely to achieve viral load suppression (below 50 copies/mL) -- 84% vs. 82%, respectively -- among the highest rates observed in recent trials of first-line HIV treatment. CD4 cell gains were also similar (192 vs. 176 cells/mm3).
Overall, 9% of rilpivirine recipients and 5% of efavirenz recipients experienced virological failure, with a larger difference in ECHO (11% vs. 4%). At ICAAC in September, researchers reported that treatment failure was linked to high baseline viral load and poor adherence (abstract H-1810).
But rilpivirine was associated with fewer side effects than efavirenz, especially central nervous system symptoms. About half as many rilpivirine recipients (16% vs. 31%) experienced moderate-to-severe adverse events considered possibly related to study drugs; 3% vs. 8%, respectively, discontinued therapy due to adverse events. Rilpivirine also had a more favorable lipid profile than efavirenz. Serum creatinine levels changed little in either group and there was no difference in QT interval changes, a type of heart rhythm abnormality.
About 60% of rilpivirine recipients and about 50% of efavirenz recipients developed new NNRTI-resistance mutations, but people taking rilpivirine were twice as likely to develop NRTI-resistance mutations.
Based on these findings, Tibotec announced that it has submitted a New Drug Application for rilpivirine to the FDA. Tibotec and Gilead Sciences are also jointly developing a single-tablet regimen containing rilpivirine plus tenofovir/emtricitabine, which was submitted for European regulatory approval in September.
Liz Highleyman (email@example.com) is a freelance medical writer based in San Francisco.
TMC278 (Rilpivirine) Stands Up to Efavirenz in Battle of First-Line NNRTIs; FDA Approval May Be Drawing Near
This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. Visit San Francisco AIDS Foundation's Web site to find out more about their activities, publications and services.
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