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ISENTRESS (raltegravir), from Merck, was as Effective as Efavirenz at Suppressing HIV Viral Load and Increasing CD4 Cell Counts in Treatment-Naïve Patients up to 144 Weeks When Used in Combination Therapy
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Merck press release
CAPE TOWN, SOUTH AFRICA, July 20, 2009 - ISENTRESS (raltegravir) tablets, an integrase inhibitor from Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., was as effective as efavirenz at maintaining viral load suppression to undetectable levels (less than 50 copies/mL) and at improving CD4 counts in previously untreated (treatment-naïve) patients through 144 weeks in a Phase II study still underway. Both medicines were administered in combination with two other anti-HIV medicines, tenofovir and lamivudine. These results were presented today at the 5th International AIDS Society's (IAS) Conference on HIV Pathogenesis, Treatment & Prevention in Cape Town, South Africa.
"We are encouraged that these data demonstrate the efficacy and tolerability profile of ISENTRESS, with less effect on lipid levels, for up to 144 weeks," said Martin Markowitz, M.D., study investigator and clinical director of the Aaron Diamond AIDS Research Center in New York. "It is important for patients at any stage of HIV to have treatment options like ISENTRESS that are effective and have a demonstrated tolerability profile in order to help them manage their disease."
On July 8, ISENTRESS was approved by the U.S. Food and Drug Administration (FDA) for use in treatment-naïve adult patients in combination with other antiretroviral (ARV) medicines for the treatment of HIV-1 infection. In markets outside the United States, where ISENTRESS is approved for treatment-experienced patients, the use of ISENTRESS in treatment-naïve patients is investigational. The expanded indication in the United States for ISENTRESS was based on analyses of plasma HIV-1 RNA levels through 48 weeks in three double-blind
controlled studies. Two of these studies were conducted in clinically advanced, three-class antiretroviral (NNRT, NRTI, PI) treatment-experienced adults and one was conducted in treatment-naïve 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 pediatric patients.
In addition, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) is expected to issue an opinion soon regarding an expanded marketing authorization of ISENTRESS in the European Union for patients starting HIV therapy for the first time, as well as all treatment-experienced patients, when used in combination with other antiretroviral medicines for the treatment of HIV-1 infection in adult patients.
ISENTRESS studied for 144 weeks in nearly 200 previously untreated adult patients
These 144-week findings are from an ongoing multi-center, dose-ranging, double-blind, randomized trial of previously untreated HIV-infected adult patients. In this study,
198 treatment-naïve, HIV-infected patients received either ISENTRESS administered orally twice daily in combination with tenofovir and lamivudine or 600 mg efavirenz dosed orally once daily in combination with the same agents. During the first 48 weeks of the study, patients were randomized to one of four dose regimens (100, 200, 400 and 600 mg twice daily). After
48 weeks, all groups receiving ISENTRESS received 400 mg dosed twice daily. The primary endpoints were reductions in HIV RNA to below 400 copies/mL and the evaluation of safety at 144 weeks. The evaluation of total cholesterol, LDL cholesterol and triglycerides were exploratory endpoints.
Viral load reductions and increase in CD4 cell counts maintained through 144 weeks
After 144 weeks of therapy, 78 percent of the 160 patients on the regimen containing ISENTRESS maintained HIV viral load suppression to below 50 copies/mL. Results were comparable for patients taking the efavirenz-based regimen, with 76 percent of the 38 patients maintaining suppression to below 50 copies/mL (95 percent CI). Eighty percent of patients receiving the regimen containing ISENTRESS maintained suppression in viral load to less than 400 copies/mL compared to 76 percent of patients taking the regimen containing efavirenz
(95 percent CI). Patients on both treatment regimens experienced increases in CD4 cell counts. At 144 weeks of treatment, the mean increase in CD4 cell counts from baseline was 252 cells/mm3 for patients receiving the regimen containing ISENTRESS and 233 cells/mm3 for patients receiving the regimen containing efavirenz.
Tolerability profile and effect on lipid levels
At 144 weeks, cumulative rates of drug-related clinical adverse experiences (AEs) were less frequent in the regimen containing ISENTRESS versus the regimen containing efavirenz (54 percent vs. 76 percent, respectively). ISENTRESS had less effect on total or LDL cholesterol, or triglycerides:
In the study, the most commonly reported AEs in the regimens containing ISENTRESS and efavirenz, respectively, were diarrhea (6.9 vs. 10.5 percent), nausea (12.5 vs.
10.5 percent), dizziness (8.8 vs. 26.3 percent), headache (8.8 vs. 23.7 percent), abnormal dreams (6.3 vs. 18.4 percent), insomnia (8.1 vs. 10.5 percent) and nightmares (0.0 vs. 10.5 percent).
About ISENTRESS
ISENTRESS is a first-in-class integrase inhibitor. ISENTRESS works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme and has demonstrated rapid antiviral activity. 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-1 replication process - protease and reverse transcriptase - but ISENTRESS is the only drug approved that inhibits the integrase enzyme.
ISENTRESS is a single 400 mg tablet taken twice daily without regard to food. ISENTRESS does not require boosting with ritonavir.
ISENTRESS is now approved in more than 80 countries worldwide for treatment-experienced adult patients. Merck is continuing to move forward with filings in additional countries around the world for use of ISENTRESS in both treatment-experienced and treatment-naïve patients.
Important safety information about ISENTRESS
ISENTRESS does not cure HIV or AIDS and does not prevent passing HIV to others.
Healthcare providers should know that immune reconstitution syndrome has been
reported in patients treated with antiretroviral therapy, which may necessitate further evaluation and treatment.
The most commonly (greater than or equal to two percent in either treatment group) reported drug-related clinical adverse experience (AE) of moderate or severe intensity in treatment-naïve patients receiving ISENTRESS and at a higher incidence compared to efavirenz was insomnia (4 percent vs. 3 percent). The most commonly (greater than or equal to 2 percent in either treatment group) reported drug-related clinical AEs of moderate or severe intensity in treatment-experienced patients receiving ISENTRESS and at a higher rate compared to placebo were headache (rate of 3 vs. 1, per 100 patient years), nausea (rate of 2 vs. 1, per 100 patient years), asthenia/weakness (rate of 2 vs. 1, per 100 patient years) and fatigue (rate of 2 vs. 1, per 100 patient years).
Creatine kinase elevations were observed in subjects who received ISENTRESS. Myopathy and rhabdomyolysis have been reported, however the relationship of ISENTRESS to these events is not known. ISENTRESS should be used with caution in patients at increased risk of myopathy or rhabdomyolysuis, such as patients receiving concomitant medication known to cause these conditions.
Drug interactions
Based on the results of drug interaction studies and the clinical trials data, no dose adjustment of ISENTRESS is required when coadministered with other ARV agents. Also, preclinical studies show that ISENTRESS is not metabolized by cytochrome P450 enzymes. The dose of ISENTRESS should be increased during coadministration with rifampin, a strong uridine diphosphate glucuronosyltransferase (UGT) 1A1, due to reduced plasma concentrations of ISENTRESS.
Merck's commitment to providing access to treatment
For more than 20 years, Merck has been at the forefront of the global response to the HIV and AIDS
pandemic through a three-pronged approach that includes working to discover, develop, and deliver breakthrough medicines; improving access to our antiretroviral medicines; and participating in partnerships that help build infrastructure and address health and development challenges, particularly in the developing world.
Since 2001, Merck has implemented a differential pricing policy that provides our ARVs at the lowest possible price at which Merck makes no profit in public sectors in the poorest countries and those hardest hit by the HIV and AIDS pandemic. Merck also provides its ARVs at significantly reduced prices in middle income countries.
About HIV and AIDS
According to the Centers for Disease Control and Prevention (CDC), in 2006 there were more than one million Americans living with HIV and AIDS. In the same year, an estimated 56,000 new cases were diagnosed in the United States.
In South Africa, there are an estimated 5.7 million adults and children living with HIV and AIDS. Furthermore, an estimated 350,000 South African adults and children died of AIDS in 2007.
An estimated 33 million people are living with HIV and AIDS worldwide, and about 2.7 million new infections occurred worldwide in 2007. AIDS is one of the top causes of infectious disease-related mortality worldwide, responsible for approximately two million deaths in 2007 alone.
About Merck & Co., Inc., Whitehouse Station, NJ, USA
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forward looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many
uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2008, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
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Full prescribing information and patient prescribing information for ISENTRESS is attached.
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