FDA Accepts sNDA for Isentress for Previously Untreated HIV-1 in Adults
Merck Announces FDA Acceptance of Supplemental New Drug Application for Isentress (raltegravir) in Adult Patients Previously Untreated for HIV-1
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Dec 12, 2008 - Merck & Co., Inc. today announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental New Drug Application (sNDA) filing for Isentress (raltegravir) Tablets for standard review. The Company is seeking United States marketing approval of Isentress in combination with other HIV medicines for treatment in adult patients who are previously untreated (naïve) for HIV. Merck expects FDA action in July 2009.
"Merck has a long-standing commitment to the research and development of novel treatments for patients infected with HIV," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. "Based on the results of our clinical program in treatment-naïve patients, we are very enthusiastic about the prospect that Isentress may now have application in the broader HIV community."
Isentress is approved 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. 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-naÃ¯ve adult patients or pediatric patients. There are no study results demonstrating the effect of Isentress on clinical progression of HIV-1 infection.
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-1 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-1 replication process – protease and reverse transcriptase – but Isentress is the only drug approved that inhibits the integrase enzyme.
Important safety information about Isentress
Isentress does not cure HIV or AIDS and does not prevent passing HIV to others. Immune reconstitution syndrome has been reported in patients treated with antiretroviral therapy, which may necessitate further evaluation and treatment.
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 rhabdomyolysis, such as patients receiving concomitant medication known to cause these conditions.
In the clinical trials involving treatment-experienced patients, the most commonly reported adverse experiences of any severity (mild, moderate or severe) for Isentress plus optimized background therapy (OBT) versus placebo plus OBT, respectively, regardless of drug relationship were diarrhea (16.6 percent vs. 19.5 percent), nausea (9.9 percent vs. 14.2 percent), headache (9.7 percent vs. 11.7 percent) and fever (4.9 percent vs. 10.3 percent).
In addition, drug-related clinical adverse events of moderate to severe intensity occurring in greater than or equal to 2.0 percent of patients were diarrhea (3.7 percent vs. 4.6 percent), nausea (2.2 percent vs. 3.2 percent) and headache (2.4 percent vs.1.4 percent) for Isentress plus OBT and placebo plus OBT, respectively. Results from pooled safety analyses from three separate studies (BENCHMRK-1, BENCHMRK-2 and a Phase II dose ranging study) in treatment-experienced patients taking 400 mg of Isentress dosed twice daily plus OBT or placebo plus OBT showed that after 24 weeks of therapy the rates of discontinuation of therapy due to adverse experiences were 2.0 percent in patients receiving Isentress plus OBT and 1.4 percent in patients receiving placebo plus OBT.
Based on the results of drug interaction studies and the clinical trials data, no dose adjustment of Isentress is required when coadministered with other antiretroviral agents. Also, preclinical studies show that Isentress is not metabolized by cytochrome P450 enzymes. Caution should be used when coadministering Isentress with strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 (e.g., rifampin) due to reduced plasma concentrations of Isentress.
In October 2007, the FDA granted Isentress accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of viral replication with HIV-1 strains resistant to multiple antiretroviral agents. Isentress is a single 400 mg tablet taken twice daily without regard to food. Isentress does not require boosting with ritonavir.
Merck HIV Research
Merck is committed to developing innovative therapies that offer advances in the treatment of infectious diseases – including HIV. Merck's efforts to develop investigational treatments for HIV and AIDS have been under way for more than 20 years and continue today. Merck began its HIV integrase inhibitor research in 1993 and was the first to demonstrate inhibition of HIV integrase in vitro and in vivo.
Prevalence of HIV and AIDS
In 2006, more than one million Americans were living with HIV and AIDS, and it is estimated that approximately more than 56,000 new cases of HIV and AIDS are diagnosed each year in the United States.
Worldwide, an estimated 33 million people are infected with HIV and AIDS, and more than two million new infections occurred in 2007.
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.
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, 2007, 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.
Isentress® is a registered trademark of Merck & Co., Inc.
Posted: December 2008