Merck Reformulates Isentress And Seeks New Indication In HIV-1

Merck announced in a press release that its Phase III trial of reformulated Isentress (raltegravir) has enrolled its first patient. The ONCEMRK trial is assessing once-daily raltegravir (1200 mg once daily), known as reformulated raltegravir (MK-0518), combined with Truvada (tenofovir/emtricitabine) vs. raltegravir (400 mg, not reformulated) twice daily in combination with Truvada in HIV-1 infected, treatment-naive participants. Researchers hypothesize that reformulated raltegravir is not inferior to standard raltegravir.

This study follows a Phase III trial of raltegravir that did not meet its endpoint. In the QDMRK study, which Merck announced in the fall of 2013, 83 percent of the 800 mg raltegravir once daily patients achieved viral suppression compared to 89 percent of the raltegravir 400 mg twice daily patients.

Merck has adjusted the formulation of Isentress with hopes of proving that once daily treatment has promise.

Jurgen Rockstroh, M.D., University of Bonn, Germany, a clinical investigator on this study, said, “Isentress has been a significant component of first-line HIV-1 treatment for more than six years, as a twice-daily component of antiretroviral therapy. We look forward to advancing our understanding of this new formulation of once-daily raltegravir with this new trial.”

Reformulated Isentress Phase III Trial

In the new trial that has enrolled its first patient, investigators are assessing results   by the proportion of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL at Week 48. The Phase III multi-center trial compares reformulated raltegravir with standard raltegravir, both combined with Truvada, in the hopes that the once daily reformulated agent proves non-inferior. Merck expects 160 centers worldwide to enroll about 750 patients for the study lasting 96 weeks. Merck expects to evaluate the primary endpoint at 48 weeks, the first half of 2016.

Isentress

Isentress is an integrase inhibitor. In its first approval of raltegravir in 2007, the FDA said it was the first in its class of HIV integrase strand transfer inhibitors. Reformulated raltegravir is a novel non-poloxamer-based formulation. The agent slows HIV-1 advancement by blocking the HIV integrase enzyme the virus needs to multiply. Isentress works best in combination with other agents. Isentress is approved in 114 countries for HIV-1. Merck continues to seek regulatory approval for multiple indications and formulations. Isentress does not cure HIV-1 infection or AIDS and severe adverse events have been reported.