WHITEHOUSE STATION, N.J., Dec. 1, 2009 – Merck & Co., Inc. announced that ISENTRESS® (raltegravir) has been recommended, in combination therapy, as one of four preferred regimens for treatment-naïve, non-pregnant patients living with HIV-1, according to updated HIV treatment guidelines issued by the United States Department of Health & Human Services (HHS). For other preferred regimens, please refer to the HHS guidelines at www.aidsinfo.nih.gov/Guidelines. The updated guidelines recommend the use of ISENTRESS in combination therapy with two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir and emtricitabine, for patients beginning treatment for the first time (treatment-naïve). The “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents” were developed by the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents, a working group of the Office of AIDS Research Advisory Council, and were issued on World AIDS Day.
The U.S. Food and Drug Administration (FDA) approved an expanded indication for ISENTRESS on July 8, 2009, to include the treatment of adult patients starting HIV-1 therapy for the first time, as well as treatment-experienced adult patients, in combination with other antiretroviral (ARV) medicines. The expanded indication for ISENTRESS was based on analyses of plasma HIV-1 RNA levels through 48 weeks in three double-blind controlled Phase III studies. Two of these studies were conducted in clinically advanced, three-class antiretroviral [nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI)] treatment-experienced adults, and one was conducted in treatment-naïve patients.
ISENTRESS is used in combination with other ARV medicines for the treatment of HIV-1 infection in adult patients. The safety and efficacy of ISENTRESS have not been established in pediatric patients. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response.
“These Guidelines play an integral role in guiding the way physicians in the U.S. treat HIV,” said Robin Isaacs, M.D., vice president, Clinical Research, Merck Research Laboratories. “As the only approved integrase inhibitor, ISENTRESS targets the HIV-1 virus in a unique way and offers physicians another option to help patients effectively lower viral loads while increasing CD4 cell counts.”
Treatment-naive indication supported by a double-blind controlled study of ISENTRESS
The treatment-naïve indication for ISENTRESS was based on analyses of 563 treatment-naïve, HIV-1 infected patients through 48 weeks in an ongoing, multi-center, double-blind, randomized, active-controlled, Phase III study called STARTMRK. Patients in the study received either 400 mg ISENTRESS administered orally twice daily or 600 mg efavirenz, one of the leading ARVs prescribed for treatment-naïve patients, dosed orally once daily. ISENTRESS and efavirenz were administered in combination with tenofovir/emtricitabine. Patients who entered the study were required to have HIV viral loads greater than 5000 copies/mL. At baseline, geometric mean HIV RNA levels for patients on the regimen including ISENTRESS was 103,205 copies/mL (n=281) and for the efavirenz regimen was 106,215 copies/mL (n=282). Mean baseline CD4 cell counts were 219 and 217 cells/mm³ for the groups receiving ISENTRESS and efavirenz, respectively.
Suppression of viral load and increase in CD4 cell counts durable through 48 weeks
In the STARTMRK trial, ISENTRESS reduced HIV-1 viral load to undetectable levels (less than 50 copies/mL) at a rate comparable to efavirenz (87 percent for ISENTRESS versus 82 percent for efavirenz); the difference in viral load reduction between the two treatment groups was 4.7 percent (95 percent CI; -1.3 percent, 10.6 percent) through 48 weeks. There were greater average increases in CD4 cell counts (176 cells/mm³ for ISENTRESS versus 150 cells/mm³ for efavirenz); the difference in mean CD4 cell count change from baseline between the two treatment groups was 25.8 (95 percent CI; 5.0, 46.5) through 48 weeks.
These efficacy results were supported by the 96-week analysis of a randomized, double-blind, controlled, dose-ranging trial, Protocol 004, in ARV treatment-naïve HIV-1 infected adult subjects comparing ISENTRESS to efavirenz, both in combination with tenofovir and lamivudine.
The HIV treatment guidelines can be obtained at www.aidsinfo.nih.gov/Guidelines.
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 ARV 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.
Tolerability profile of ISENTRESS in treatment-naïve patients
In treatment-naïve patients receiving ISENTRESS, the most commonly (greater than or equal to two percent in either treatment group) reported drug-related clinical adverse event (AE) of moderate or severe intensity and at a higher incidence compared to efavirenz was insomnia (four percent versus three percent).
In treatment-experienced patients receiving ISENTRESS, the most commonly (greater than or equal to two 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 three versus one, per 100 patient years), nausea (rate of two versus one, per 100 patient years), asthenia/weakness (rate of two versus one, per 100 patient years) and fatigue (rate of two versus one, per 100 patient years).
Dosing and administration
ISENTRESS is a single 400 mg tablet taken twice daily without regard to food. The dose of ISENTRESS should be increased during coadministration with rifampin to 800 mg twice daily.
Drug interactions
Coadministration with strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 may reduce plasma concentrations of ISENTRESS. 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.
About ISENTRESS
ISENTRESS is the first medicine to be approved in a class of ARV drugs called integrase inhibitors. 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. Other HIV-1 drugs in use inhibit two other enzymes critical to the HIV-1 replication process – protease and reverse transcriptase – but ISENTRESS is the only approved drug that inhibits the integrase enzyme.
ISENTRESS is now approved in more than 85 countries worldwide for treatment-experienced adult patients with evidence of viral replication, and is approved in the U.S., Japan, Canada, the European Union, Norway and Iceland for treatment-naïve and 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.
Patient assistance programs in the U.S.
Merck recently launched a co-pay assistance program in the U.S. for eligible patients on ISENTRESS who are commercially insured and have co-pays or coinsurance above $30 up to a maximum of $400 per month. With this program, eligible patients can receive savings off their out-of-pocket costs for up to one year. Information about the co-pay assistance program can be obtained by calling 866-350-9232 or at www.isentress.com.
In addition, for eligible patients with HIV, Merck provides patient assistance to ensure access to ISENTRESS through a program called SUPPORT™. The SUPPORT Program helps patients who have been prescribed ISENTRESS by providing personalized support and patient advocacy regarding individual reimbursement issues. The Program can also provide patient assistance which may provide ISENTRESS free of charge to eligible patients. Information about the SUPPORT Program can be obtained by calling 1-800-850-3430 or at www.isentress.com.
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.
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
Today's Merck is working to help the world be well. Through our medicines, vaccines, biologic therapies, and consumer and animal products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching programs that donate and deliver our products to the people who need them. Merck. Be Well. For more information, visit www.merck.com.
Forward Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period, due to, among other things, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2008 Annual Report on Form 10-K, Schering-Plough’s Quarterly Report on Form 10-Q for the quarterly period ended Sept. 30, 2009, the proxy statement filed by Merck on June 25, 2009 and each company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). |
