Merck Frosst Canada Ltd. is pleased to announce that (Pr)ISENTRESS(R) (raltegravir) is now indicated for use in treatment-naïve HIV-1 infected adults in combination with other antiretroviral agents. The approval of ISENTRESS(R) (raltegravir) as part of a first line regimen is in addition to the previously approved use in treatment-experienced adults living with HIV-AIDS who have developed resistance to multiple antiretroviral agents. This new indication is testament to its efficacy and good tolerability profile.
"The availability of raltegravir as part of earlier HIV drug combinations is significant news for newly treated patients because we are able to decrease viral load without debilitating side effects," said Dr. Colin Kovacs, HIV specialist and Assistant Professor, University of Toronto. "Having this potent treatment as part of a first line course of therapy provides us with the option to use raltegravir in a broader spectrum of patients."
This indication is based on the evidence of efficacy of ISENTRESS(R) (raltegravir) from the analysis of 48-week data from three ongoing, randomized, double-blind, placebo-controlled trials, BENCHMRK 1 and BENCHMRK 2 (Protocols 018 and 019), in antiretroviral treatment-experienced HIV-1 infected adult patients and the analysis of 48-week data from an ongoing, randomized, double blind, active-control trial, STARTMRK (Protocol 021). These efficacy results were supported by the 48-week analysis of a randomized, double-blind, controlled, dose-ranging trial, Protocol 005, in antiretroviral treatment-experienced HIV-1 infected adult patients and 96-week analysis of a randomized, double-blind, controlled, dose-ranging trial, Protocol 004, in antiretroviral treatment-naïve HIV-1 infected adult patients.
In the STARTMRK study of treatment-naïve patients, raltegravir was found to be as effective as efavirenz (one of the standard antiretrovirals prescribed for treatment-naïve patients) at suppressing viral load and restoring immune system function through 48 weeks. Both medicines were administered in combination with tenofovir and emtricitabine.
Potent and durable efficacy in treatment-naive patients
The treatment-naïve indication for raltegravir in combination therapy was based on analyses of 563 treatment-naïve, HIV-1-infected patients through 48 weeks in an ongoing, multi-centre, double-blind, randomised, active-controlled, Phase III study called STARTMRK. Patients in the study received either 400 mg raltegravir>
In the STARTMRK trial, the regimen including raltegravir reduced HIV-1 viral load to undetectable levels (less than 50 copies/mL) at a rate comparable to the regimen containing efavirenz (86 percent of patients treated with raltegravir versus 82 percent of patients treated with efavirenz, both in combination therapy); the difference in viral load reduction between the two treatment groups was 4.2 percent (95 percent CI; -1.92, 10.3) through 48 weeks. There were greater average increases in CD4 cell counts for raltegravir in combination therapy (189 cells/mm) versus efavirenz in combination therapy (163 cells/mm); the difference in mean CD4 cell count change from baseline between the two treatment groups was 25.8 (95 percent CI; 4.4, 47.2) through 48 weeks. This difference though was not statistically significant.
There were fewer overall side effects with raltegravir through 48 weeks in the STARTMRK trial. Nervous system side effects were reported significantly less frequently in the group receiving raltegravir compared to the group receiving efavirenz. In the group receiving raltegravir, the percentage of patients with one or more central nervous system symptoms at week 48 was 26.0% compared to 58.5% in the group receiving efavirenz. Through 48 weeks of therapy raltegravir also demonstrated less impact on lipid levels, including total, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels compared to the group treated with efavirenz.
The 48 week efficacy results were supported by the 96-week analysis of a randomised, double-blind, controlled, dose-ranging trial, Protocol 004, in antiretroviral treatment-naïve HIV-1-infected adult subjects comparing raltegravir to efavirenz, both in combination with tenofovir and lamivudine.