New Phase III Study in Previously Untreated HIV Patients Showed Merck's ISENTRESS® Reduced HIV Viral Load to Undetectable Levels, Comparable to Efavirenz, When Taken in Combination with Other Medicines

Business Wire, Oct 26, 2008

Study Showed ISENTRESS Increased CD4 Cells More Than Efavirenz, with Significantly Fewer Side Effects

WASHINGTON -- In a new Phase III study that compared Merck & Co., Inc.'s HIV integrase inhibitor ISENTRESS([R]) (raltegravir) to efavirenz [one of the leading antiretrovirals prescribed for previously untreated (treatment-naove) HIV-infected patients], ISENTRESS reduced HIV viral load to undetectable levels (less than 50 copies/mL) in 86 percent of patients compared to 82 percent of patients treated with efavirenz in previously untreated HIV patients at Week 48. Both medicines were taken in combination with tenofovir/emtricitabine. Patients taking ISENTRESS had a greater increase in CD4 cell counts, an average increase of 189 cells/mm3, compared to patients taking efavirenz who had an average increase of 163 cells/mm3at Week 48. In addition, drug-related adverse events of any severity occurred in fewer patients (44 percent vs. 77 percent; p<0.001) treated with ISENTRESS. The use of ISENTRESS in treatment-naove patients is investigational. These 48 week findings were presented today at the late-breaker session of the joint 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46th Annual Meeting in Washington, D.C.

"This study showed that when paired with other anti-HIV medicines, ISENTRESS lowered the amount of virus in the blood to below detectable (less than 50 copies/mL) levels in over 8 out of 10 treatment-naove patients and had fewer side effects than the standard of care," said Daniel S. Berger, M.D., clinical associate professor, College of Medicine University of Illinois at Chicago and medical director of NorthStar Medical Center. "These results further demonstrate that, if approved for such use, ISENTRESS may be another important option for patients when first initiating HIV therapy."

ISENTRESS is the first integrase inhibitor approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of viral replication with HIV-1 strains resistant to multiple antiretroviral agents. This indication is based on analyses of plasma HIV-1 RNA levels up through 24 weeks in two controlled studies of ISENTRESS. These studies were conducted in clinically advanced, three-class antiretroviral [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] treatment-experienced adults. In these studies the use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response. The safety and efficacy of ISENTRESS have not been established in treatment-naove adult or pediatric patients. There are no study results demonstrating the effect of ISENTRESS on clinical progression of HIV-1 infection.

ISENTRESS studied in more than 500 previously untreated HIV patients in Phase III trial

These findings presented today are from an ongoing multi-center, double-blind, randomized, active-controlled Phase III trial of previously untreated HIV-infected patients called STARTMRK. In this study, 563 treatment-naove, HIV-infected patients received either 400 mg ISENTRESS administered orally twice daily in combination with tenofovir/emtricitabine or 600 mg efavirenz dosed orally once daily in combination with the same agents. The primary endpoints were reductions in HIV RNA to less than 50 copies/mL and an evaluation of safety and tolerability at Week 48. Secondary endpoints included antiretroviral activity as measured by the proportion of patients achieving HIV RNA <400 copies/mL and change from baseline in CD4 cell counts at Week 48. An additional secondary safety endpoint was the proportion of patients experiencing nervous system symptoms through week eight.

Suppression of viral load and increase in CD4 cell counts maintained through 48 weeks

At baseline, geometric mean HIV RNA levels for patients on the regimen including ISENTRESS was 103,205 copies/mL (n=281) and for the efavirenz regimen was 106,215 copies/mL (n=282). Mean baseline CD4 cell counts were 219 and 217 cells/mm3 for the groups receiving ISENTRESS and efavirenz, respectively.

After 48 weeks of treatment, 86 percent of patients receiving the regimen with ISENTRESS achieved reductions in HIV RNA levels below 50 copies/mL. Results were comparable for patients taking the efavirenz regimen, with 82 percent of patients achieving reductions in HIV RNA levels below 50 copies/mL in the same time period. Similarly, 90 percent of patients receiving the regimen containing ISENTRESS maintained reductions in HIV RNA levels to below 400 copies/mL compared to 86 percent of patients taking the regimen containing efavirenz. Time to virologic response was significantly shorter for patients taking ISENTRESS compared to those taking the efavirenz regimen, confirming the rapid viral load reductions demonstrated by ISENTRESS in previous trials. At week eight, 74 percent of patients receiving the regimen with ISENTRESS achieved HIV RNA levels below 50 copies/mL compared to 38 percent of patients receiving the regimen with efavirenz.