Merck & Co., Inc., announced that the U.S. Food and Drug Administration (FDA) granted ISENTRESS TM (raltegravir) tablets accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and 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 [pronounced i-sen-tris]. 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.
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-naïve adult patients or pediatric patients. There are no study results demonstrating the effect of ISENTRESS on clinical progression of HIV-1 infection. Longer term data will be required before the FDA can consider traditional approval for ISENTRESS.
ISENTRESS is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors. ISENTRESS works by inhibiting the insertion of HIV DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV replication process – protease and reverse transcriptase – but ISENTRESS is the only drug approved that inhibits the integrase enzyme.
The FDA’s decision was based on a 24-week analysis of clinical trials in which ISENTRESS in combination with optimized background therapy (OBT) in treatment-experienced patients, provided significant reductions in HIV RNA viral load and increases in CD4 cell counts.
“The development of ISENTRESS is a significant milestone in the history of HIV/AIDS therapy because we now have a drug that’s potent against another key enzyme essential for viral replication,” said Joseph J. Eron Jr., M.D., professor of medicine, Division of Infectious Diseases, UNC Chapel Hill School of Medicine. “It’s important for physicians to know that ISENTRESS should always be used in combination with other active agents.”
Data from two ongoing Phase III multi-center, double-blind, randomized, placebo-controlled studies (BENCHMRK-1 and BENCHMRK-2) in 699 treatment-experienced adult patients with documented resistance to at least one drug in each of three classes (NRTIs, NNRTIs and PIs) of antiretroviral therapies showed that ISENTRESS 400 mg dosed twice daily in combination with OBT was significantly more effective at both reducing levels of HIV viral RNA and increasing CD4 cell counts in these patients living with HIV, when compared to a regimen of placebo plus OBT.
Pooled analyses from the two Phase III studies showed that after 24 weeks of therapy, 75.5 percent of patients (216 out of 286) receiving ISENTRESS in combination with OBT achieved HIV viral RNA load reduction to below 400 copies/mL compared to 39.3 percent of patients (59 out of 150) receiving placebo plus OBT. In addition, after 24 weeks of therapy, 62.6 percent of patients (179 out of 286) receiving ISENTRESS plus OBT achieved viral load reduction to below 50 copies/mL compared to 33.3 percent of patients (50 out of 150) receiving placebo plus OBT. After 24 weeks of therapy, increases in CD4 cell counts from baseline were 89 and 35 cells/mm3 for patients receiving ISENTRESS plus OBT and for those receiving placebo plus OBT, respectively.