Isentress (raltegravir) from MSD, First Integrase Inhibitor, Approved by the European Union Commission

First-in-Class Therapy Addresses Medical Need for New Treatment Options in Treatment-Experienced Patients

WHITEHOUSE STATION, N.J. -- December 21, 2007 -- (BUSINESS WIRE) -- Merck Sharp & Dohme (MSD) announced today that Isentress (raltegravir) has been granted a license from the European Union Commission by way of a decision for use in combination with other antiretroviral medicinal products for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy (ART). The Commission's decision is applicable to the 27 Member States of the European Union (EU), including France, Germany, Italy, Spain and the United Kingdom. Separate national licenses, based on the Commission's decision, will also be issued in European Economic Area Member States Iceland and Norway. Raltegravir is the first approved integrase inhibitor, a new class of ART that works by targeting the integrase enzyme, which is essential for HIV replication.

The Commission's decision, reflecting the positive opinion of the European Medicines Agency, was based on efficacy and safety data from two double-blind, placebo-controlled trials of 24 weeks duration in treatment-experienced patients. In these studies raltegravir, in combination with optimized background therapy (OBT), significantly reduced HIV RNA viral load (p < 0.001), and significantly increased CD4 cell counts (p < 0.001). The efficacy and safety of raltegravir have not been established in treatment-naïve adult patients or pediatric patients, although studies in these populations are underway.

"Raltegravir is an important new advancement in the treatment of HIV, because it is the first therapy in a new class of drugs that attacks the virus in a completely different way from other available medicines," said Ken Frazier, executive vice president and president, Global Human Health, Merck & Co., Inc. "This approval marks another milestone in MSD's continued commitment to combating HIV and AIDS by conducting research for breakthrough medicines, developing business models that help our products reach as many people as possible, and participating in partnerships to help build infrastructure and address health and development challenges around the world."

Despite the availability of drugs to treat HIV and AIDS, the pandemic continues. In the EU, nearly 250,000 cases of HIV have been reported since 2002, according to the European Centre for the Epidemiological Monitoring of HIV and AIDS. Additionally, resistance to current HIV therapies in treatment-experienced patients has been noted in numerous international studies, suggesting that resistance to at least one class of antiretroviral agents may be as high as 76 percent. The World Health Organization (WHO) has called resistance an emerging public health concern and has partnered with the International AIDS Society to develop the Global HIV Drug Resistance Surveillance Network to track emerging resistance patterns in developing and developed countries.

"Treatment-experienced HIV patients have limited options for therapies that are well-tolerated and can reduce viral loads while boosting CD4 counts," said Jürgen Rockstroh, professor of medicine and head of the HIV Outpatient Clinic, University of Bonn, Germany. "The approval of raltegravir in the EU represents a significant scientific advancement, but more importantly, it addresses a much-needed evolution in the treatment of HIV and AIDS."

Reduction in viral load and increase in CD4 cell counts

Raltegravir is being studied in 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 [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] of ARTs. Raltegravir 400 mg taken twice daily in combination with OBT was significantly (p < 0.001) more effective at both reducing levels of HIV RNA and increasing CD4 cell counts in these patients, when compared to a regimen of placebo plus OBT. The efficacy responses were evaluated based upon the 699 patients from the pooled studies who had completed 24 weeks of treatment or discontinued earlier.

The studies showed that after 24 weeks of therapy, 75 percent of patients (347 out of 462) receiving raltegravir in combination with OBT achieved HIV RNA load reduction to below 400 copies/mL, compared to 40 percent of patients (95 out of 237) receiving placebo plus OBT. In addition, after 24 weeks of therapy, 63 percent of patients (289 out of 462) receiving raltegravir plus OBT achieved viral load reduction to below 50 copies/mL, compared to 34 percent of patients (80 out of 237) receiving placebo plus OBT. After 24 weeks of therapy, increases in CD4 cell counts from baseline were 84 and 37 cells/mm3 for patients receiving raltegravir plus OBT and for those receiving placebo plus OBT, respectively.

Raltegravir is a single 400 mg tablet taken twice daily without regard to food. Raltegravir does not require boosting with ritonavir. In Phase II and III clinical trials, the side effect profile was comparable with placebo. The most common side effects are diarrhea, nausea, headache, and pyrexia.

About raltegravir

Raltegravir is the first in a new class of antiretroviral agents called integrase inhibitors. Raltegravir works by inhibiting the insertion of the HIV DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function blocks the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit the other two enzymes critical to the HIV replication process - protease and reverse transcriptase - but raltegravir is the only drug approved that inhibits integrase.