Canada approves ISENTRESS(R) for adults starting HIV treatment

MONTREAL , Oct. 20 /CNW Telbec/ - Merck Frosst Canada Ltd. is pleased to announce that (Pr)ISENTRESS(R) (raltegravir) is now indicated for use in treatment-naïve HIV-1 infected adults in combination with other antiretroviral agents.(1) The approval of ISENTRESS(R) (raltegravir) as part of a first line regimen is in addition to the previously approved use in treatment-experienced adults living with HIV-AIDS who have developed resistance to multiple antiretroviral agents. This new indication is testament to its efficacy and good tolerability profile.

"The availability of raltegravir as part of earlier HIV drug combinations is significant news for newly treated patients because we are able to decrease viral load without debilitating side effects," said Dr. Colin Kovacs , HIV specialist and Assistant Professor, University of Toronto . "Having this potent treatment as part of a first line course of therapy provides us with the option to use raltegravir in a broader spectrum of patients."

This indication is based on the evidence of efficacy of ISENTRESS(R) (raltegravir) from the analysis of 48-week data from three ongoing, randomized, double-blind, placebo-controlled trials, BENCHMRK 1 and BENCHMRK 2 (Protocols 018 and 019), in antiretroviral treatment-experienced HIV-1 infected adult patients and the analysis of 48-week data from an ongoing, randomized, double blind, active-control trial, STARTMRK (Protocol 021). These efficacy results were supported by the 48-week analysis of a randomized, double-blind, controlled, dose-ranging trial, Protocol 005, in antiretroviral treatment-experienced HIV-1 infected adult patients and 96-week analysis of a randomized, double-blind, controlled, dose-ranging trial, Protocol 004, in antiretroviral treatment-naïve HIV-1 infected adult patients.(1)

In the STARTMRK study of treatment-naïve patients, raltegravir was found to be as effective as efavirenz (one of the standard antiretrovirals prescribed for treatment-naïve patients) at suppressing viral load and restoring immune system function through 48 weeks. Both medicines were administered in combination with tenofovir and emtricitabine.

Potent and durable efficacy in treatment-naive patients

The treatment-naïve indication for raltegravir in combination therapy was based on analyses of 563 treatment-naïve, HIV-1-infected patients through 48 weeks in an ongoing, multi-centre, double-blind, randomised, active-controlled, Phase III study called STARTMRK. Patients in the study received either 400 mg raltegravir (n=281) administered orally twice daily or 600 mg oral efavirenz once daily (n=282) in combination with tenofovir/emtricitabine.(2)

In the STARTMRK trial, the regimen including raltegravir reduced HIV-1 viral load to undetectable levels (less than 50 copies/mL) at a rate comparable to the regimen containing efavirenz (86 percent of patients treated with raltegravir versus 82 percent of patients treated with efavirenz, both in combination therapy); the difference in viral load reduction between the two treatment groups was 4.2 percent (95 percent CI; -1.92, 10.3) through 48 weeks. There were greater average increases in CD4 cell counts for raltegravir in combination therapy (189 cells/mm(3)) versus efavirenz in combination therapy (163 cells/mm(3)); the difference in mean CD4 cell count change from baseline between the two treatment groups was 25.8 (95 percent CI; 4.4, 47.2) through 48 weeks. This difference though was not statistically significant.(2)

There were fewer overall side effects with raltegravir through 48 weeks in the STARTMRK trial.(2) Nervous system side effects were reported significantly less frequently in the group receiving raltegravir compared to the group receiving efavirenz. In the group receiving raltegravir, the percentage of patients with one or more central nervous system symptoms at week 48 was 26.0% compared to 58.5% in the group receiving efavirenz. Through 48 weeks of therapy raltegravir also demonstrated less impact on lipid levels, including total, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels compared to the group treated with efavirenz.(1)

The 48 week efficacy results were supported by the 96-week analysis of a randomised, double-blind, controlled, dose-ranging trial, Protocol 004, in antiretroviral treatment-naïve HIV-1-infected adult subjects comparing raltegravir to efavirenz, both in combination with tenofovir and lamivudine.(3)

About ISENTRESS(R)

ISENTRESS(R) (raltegravir) is approved by Health Canada for use in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adult patients.

Raltegravir attacks the HIV virus in a way that's different than other available antiretroviral treatments. It is the only drug approved that blocks the action of integrase, an enzyme that is critical to the HIV replication process. By targeting the integrase enzyme, raltegravir limits the ability of the virus to replicate and infect new cells. Used in combination with other antiretroviral agents, raltegravir has been shown to be effective at both reducing viral load to undetectable levels and raising CD4 cell count in people living with HIV-AIDS in people starting HIV therapy for the first time and in people who were previously treated with other antiretroviral agents. Raltegravir is administered as a single 400 mg tablet taken twice daily with or without food with other HIV medications. Raltegravir does not require boosting with ritonavir.

About HIV-AIDS

    
    - As of June 2006, 61,423 people in Canada have tested positive for HIV.
      Of these people, 83.6% are male and 16.4% are female.(4)
    - Of the estimated 58,000 people living with HIV/AIDS at the end of 2005
      in Canada(5), approximately 27% were unaware of their HIV status(6).
    - The number of new HIV infections in 2005 has not decreased and may have
      increased slightly compared to 2002.(5)
    

Merck Frosst's commitment to HIV research

Merck Frosst is committed to developing innovative therapies that offer advances in the treatment of infectious diseases - including HIV. The Company's efforts to develop investigational treatments for HIV-AIDS have been under way for more than 20 years and continue today. We began our HIV integrase inhibitor research in 1993 and were the first to demonstrate inhibition of HIV integrase in vitro and in vivo.

About Merck Frosst Canada Ltd.

At Merck Frosst, patients come first. Merck Frosst Canada Ltd. is a research-driven pharmaceutical company. Merck Frosst discovers, develops and markets a broad range of innovative medicines and vaccines to improve human health. The Merck Frosst Centre for Therapeutic Research, one of the largest biomedical research facilities in Canada , has the mandate to discover new therapies for the treatment of infectious diseases. More information about Merck Frosst and ISENTRESS(R) is available at http://www.merckfrosst.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 cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007 , and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

    
    ISENTRESS(R) is a registered trademark of Merck & Co., Inc., used under
    license.

    References:

    -------------------------------
    (1) Product Monograph. (Pr)ISENTRESS(R) raltegravir tablets 400 mg (as
        raltegravir potassium) Human immunodeficiency virus integrase strand
        transfer inhibitor. September 24, 2009.

    (2) Lennox, Jeffrey, L. et al. Safety and efficacy of raltegravir-based
        versus efavirenz-based combination therapy in treatment-naïve
        patients with HIV-1 infection: a multicentre, double-blind randomised
        controlled trial. The Lancet 2009: 374(9692): 796 - 806.

    (3) Markowitz, M, et al. Sustained Antiretroviral Effect of Raltegravir
        After 96 Weeks of Combination Therapy in Treatment-Naïve Patients
        With HIV-1 Infection. Acquir Immune Defic Syndr _ Volume 00, Number
        0, Month 0, 2009

    (4) Public Health Agency of Canada. Surveillance and Risk Assessment
        Division, Centre for Infectious Disease Prevention and Control,
        Public Health Agency of Canada. (2006). HIV and AIDS in Canada;
        Surveillance Report to June 30, 2006. November 2006 Available at:
        http://www.phac-aspc.gc.ca/publicat/aids-sida/haic-vsac0606/index-eng.php.
        Accessed on October 5, 2009.

    (5) Public Health Agency of Canada. Surveillance and Risk Assessment
        Division, Centre for Infectious Disease Prevention and Control.
        (2007). HIV/AIDS Epi Updates, 2007. Available at:
        http://www.phac-aspc.gc.ca/aids-sida/populations-eng.php#.pl.
        Accessed on October 5, 2009.

    (6) Boulos D, Yan P, Schanzer D, Remis RS and Archibald C. Estimates of
        HIV prevalence and incidence in Canada, 2005. Can Commun Dis Rep
        2006; 32(15): 165-174. Available at:
        http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06pdf/cdr3215.pdf.
        Accessed on October 5, 2009.
    

For further information: Fiona Robinson, Hill & Knowlton Canada, [phone], [email protected]; Natacha Raphael, Merck Frosst Canada Ltd., [phone], [email protected]