Clinical Data
The study found that after 48 weeks of treatment, 1200 mg raltegravir (given as 2 x 600 mg once-daily) was statistically non-inferior (88.9 percent, 472/531) to the marketed formulation approved dose of ISENTRESS 400 mg twice-daily (88.3 percent, 235/266), each in combination therapy with TRUVADA® (emtricitabine/tenofovir disoproxil fumarate); with a treatment difference [95 percent confidence interval] of 0.5 (-4.2, 5.2), as assessed by the proportion of patients achieving less than 40 copies/mL of HIV RNA. Furthermore, the study showed comparable rates of reported drug-related clinical adverse events and rates of discontinuation between the two treatment groups.


Data for once-daily investigational formulation of ISENTRESS shows comparable efficacy to approved twice-daily formulation at 48 weeks in Phase 3 pivotal trial, ONCEMRKThe primary efficacy objective of ONCEMRK is the proportion of patients achieving HIV RNA less than 40 copies/mL at Week 48. At 48 weeks, the regimen containing a once-daily dose of 1200 mg ISENTRESS (given as 2 x 600 mg once-daily) achieved similar rates of viral suppression as those patients receiving the regimen containing 400 mg ISENTRESS twice-daily (both regimens in combination with TRUVADA®) of 88.9 percent (472/531) and 88.3 percent (235/266), respectively; with a treatment difference [95 percent confidence interval] of 0.5 (-4.2, 5.2). Additionally, more than 50 percent of patients in either treatment arm achieved viral suppression of less than 40 copies/mL of HIV RNA after 4 weeks of treatment; 53.5 percent (284/531) for the once-daily arm vs. 51.9 percent (138/266) for the twice-daily arm, respectively; with a treatment difference [95 percent confidence interval] of 1.3 [-5.1, 7.7].Also, comparable efficacy was achieved for patients with baseline viral RNA greater than 100,000 copies/mL (86.7 percent [124/143] with HIV RNA less than 40 copies/mL for the once-daily formulation vs. 83.8 percent [62/74] for the twice-daily formulation, respectively); with a treatment difference [95 percent confidence interval] of 2.9 [-6.5, 14.1] Both regimens showed similar rates of reported drug-related clinical adverse events (24.5 percent [n=130] vs. 25.6 percent [n=68], respectively; with a treatment difference [95 percent confidence interval] of -1.1 (-7.6, 5.1). Overall, there was a low rate of discontinuation between the two treatment groups (7.7 percent for the once-daily formulation [n=41] vs. 8.9 percent for the twice-daily formulation [n=24]) and treatment-emergent viral mutations leading to treatment resistance were found in less than 1 percent (5/531) of patients receiving the once-daily formulation.Results from this study showed increases in CD4 counts for the once-daily arm (232 cells/mm3) comparable to the twice-daily arm (234 cells/mm3) at Week 48.