Raltegravir labeling updated with long-term data from Phase 3 HIV trial
The drug labeling for Isentress (raltegravir; Merck) and Isentress HD (raltegravir; Merck) have been updated to include Week 96 data from the ONCEMRK trial which compared Isentress HD once daily vs Isentress twice daily, both in combination with other antiretrovirals (emtricitabine + tenofovir disoproxil fumarate) in treatment-naive HIV-1 infected patients with HIV-1 RNA ≥1000 copies/mL.
Isentress and Isentress HD are HIV-1 integrase strand transfer inhibitors (INSTI) approved in combination with other antiretroviral drugs to treat HIV-1 infection in adults. Isentress is indicated in combination with other antiretroviral drugs to treat HIV-1 infection in pediatric patients weighing ≥2kg; Isentress HD is indicated for use in pediatric patients weighing ≥40kg.
Findings from the Phase 3 randomized, double-blind, active-controlled trial (N=797) showed that the proportion of patients with HIV RNA <40 copies/mL was 82% in the Isentress HD 1200mg once daily group vs 80% in the Isentress 400mg twice daily group at Week 96 (treatment difference 1.4%, 95% CI: -4.4%, 7.3%).
Regarding safety, the occurrence of Grade ≥2 lab abnormalities representing a worsening Grade from baseline of AST, ALT or total bilirubin was seen in 27%, 40% , and 13% of co-infected (with HBV and/or HCV) patients who received Isentress HD, respectively, compared with 7%, 5%, and 3% of all other patients who received Isentress HD, respectively. These findings at Week 96 were similar to that seen through Week 48.
Primary raltegravir resistance substitutions were seen in on treatment isolates taken from 4 (N155H and E92Q) of 14 virologic failure patients in the Isentress HD arm vs 2 (N155H and T97A) of 6 virologic failure patients in the Isentress arm. Other integrase substitutions included L74M, Q95K, V151I, E170A, I203M, and D232N. At Week 96, detection of raltegravir resistance was not different between the Isentress HD and Isentress arms in patients who were failing treatment and had evaluable resistance data (28.6% vs 33.3%).
Isentress is available as 25mg and 100mg chewable tablets and 400mg film-coated tablets. Isentress HD is available as 600mg film-coated tablets.