ISENTRESS(TM) (raltegravir), Merck Frosst's First in Class Integrase Inhibitor, Reduced HIV Viral Load and Increased CD4 Cell Counts Through 96 Weeks in Treatment-Naive HIV-Infected Patients When Taken With Other Anti-HIV Medicines



    Efficacy and Tolerability Profile Consistent With Results Seen in
    Treatment-Experienced Patients

    KIRKLAND, QC, Aug. 5 /CNW Telbec/ - ISENTRESS(TM) (raltegravir), Merck
Frosst's first-in-class integrase inhibitor, in combination with two other
anti-HIV medicines, reduced HIV viral load to undetectable levels (less than
50 copies/mL) (83 percent of patients) comparable to efavirenz (STOCRIN(R))
also combined with the same anti-HIV medicines (84 percent of patients) in
previously untreated (treatment-naive), HIV-infected patients through 96 weeks
of treatment. Patients taking raltegravir experienced a mean increase in CD4
cell counts of 221 cells/mm3 and experienced no adverse impact on total or
low-density lipoprotein (LDL) cholesterol, or triglycerides. Results from this
ongoing Phase II study were presented today at the 17th International AIDS
Conference (AIDS 2008) in Mexico City, Mexico.(1)
    The use of raltegravir in treatment-naive patients is investigational. In
2007 Health Canada granted a Notice of Compliance with Conditions (NOC/c)(2)
to raltegravir 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 who show resistance to multiple
antiretroviral agents.(3)
    "I am using raltegravir with many of my treatment-experienced patients
and am encouraged by the results reported today," said Christos Tsoukas, M.D.,
Professor of Medicine and Director, Division of Clinical Immunology & Allergy
at McGill University and study investigator. "The tolerability results are
very good. In particular the lack of negative effects on lipids is extremely
important. This study brings us one step closer to being able to add
raltegravir to our treatment-naive patient armamentarium."
    Approximately 58,000 Canadians are living with HIV/AIDS.

    Raltegravir studied in nearly 200 previously untreated patients

    These findings are from an ongoing multi-centre, dose-ranging,
double-blind, randomised trial of previously untreated HIV-infected patients.
In this study, 198 treatment-naive, HIV-infected patients received either
raltegravir 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, four dose regimens of
raltegravir (100, 200, 400 and 600 mg twice daily) were studied. After
48 weeks, all raltegravir groups received 400 mg dosed twice daily.(1)

    Reduction in viral load and increase in CD4 cell counts maintained
    through 96 weeks of treatment with raltegravir

    At baseline, geometric mean HIV RNA for patients on the combined
raltegravir arm of the study was approximately 55,000 copies/mL (n=160) and
for the efavirenz arm was approximately 68,000 copies/mL (n=38). Mean baseline
CD4 cell counts were 305 and 280 cells/mm3 for the raltegravir and efavirenz
groups, respectively.(1)
    After 96 weeks of therapy, 83 percent of patients on the
raltegravir-based regimen achieved reductions in HIV RNA levels below 50
copies/mL. Results were comparable for patients taking the efavirenz-based
regimen, with 84 percent of patients achieving reductions in HIV RNA levels
below 50 copies/mL in the same time period. Similarly, 84 percent of patients
receiving the regimen containing raltegravir maintained reductions in HIV RNA
levels to below 400 copies/mL compared to 84 percent of patients taking the
regimen containing efavirenz.
    Patients on both treatment regimens experienced substantial increases in
CD4 cell counts. At 96 weeks of treatment, the mean increase from baseline in
CD4 cell count was 221 cells/mm3 for the raltegravir group and 232 cells/mm3
for the efavirenz group.(1)

    Favourable tolerability profile and minimal effect on lipid levels
    demonstrated

    Both treatment regimens were generally well tolerated. Raltegravir had no
adverse effect on total and LDL cholesterol, or triglycerides.(1) The mean
changes from baseline at Week 96 for raltegravir and efavirenz, respectively,
were +1.1 mg/dL and +24.0 mg/dL (p=0.002) for total cholesterol; -5.8 mg/dL
and +4.4 mg/dL (p=0.045) for LDL cholesterol; +7.4 mg/dL and +13.0 mg/dL
(p=0.017) for HDL cholesterol; -10.8 mg/dL and +13.4 mg/dL (p=0.145) for
triglycerides; and -0.7 mg/dL and -0.7 mg/dL (P=0.689) for total: HDL ratio.
    Clinical adverse experiences were generally mild to moderate. The most
commonly reported adverse experiences in the raltegravir and efavirenz groups,
respectively, were diarrhea (6.9 percent versus 10.5 percent), nausea
(12.5 versus 13.2 percent), dizziness (8.8 versus 28.9 percent), headache
(8.8 percent versus 23.7 percent), abnormal dreams (6.3 percent versus
18.4 percent), insomnia (8.1 percent versus 10.5 percent) and nightmares (0
percent versus 10.5 percent). Neuropsychiatric adverse events, which included
abnormal dreams, depression, nightmare and suicidal thoughts, were reported
less frequently in the raltegravir group compared to the efavirenz group,
occurring respectively in 16 versus 32 percent of patients through week 96;
most of these had occurred earlier in the study by week 48.(1)

    About raltegravir

    Raltegravir is the first medicine to be approved in a new class of
antiretroviral drugs called integrase inhibitors. Raltegravir works by
inhibiting the insertion of HIV-1 DNA into human DNA by the integrase
enzyme.(4) Inhibiting integrase from performing this essential function limits
the ability of the virus to replicate and infect new cells.(4) There are drugs
in use that inhibit two other enzymes critical to the HIV-1 replication
process - protease and reverse transcriptase - but raltegravir is the only
drug approved that inhibits the integrase enzyme.(5)
    Raltegravir is a single 400 mg tablet taken twice daily without regard to
food. Raltegravir does not require boosting with ritonavir.
    Since 2007, raltegravir has received regulatory approval in more than
50 countries around the world 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.

    Our Commitment to HIV research

    We are 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.
    Raltegravir is one part of our history in HIV research, which includes
the development of CRIXIVAN(R) (indinavir sulfate), a PI; STOCRIN(R)+
(efavirenz), an NNRTI; and research currently underway on additional treatment
options.

    About Merck Frosst

    At Merck Frosst, patients come first. Merck Frosst Canada Ltd. is a
research-driven pharmaceutical company discovering, developing and marketing a
broad range of innovative medicines and vaccines to improve human health.
Merck Frosst is one of the top 25 R&D investors in Canada, with an investment
of close to $110 million in 2007. More information about Merck Frosst 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 1
of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic
reports on Form 10-Q and Form 8-K, which the Company incorporates by reference

    ISENTRESS(TM) Trademark Merck & Co., Inc. Used under license
    CRIXIVAN(R) (R)Trademark of Merck & Co., Inc. Used under license.
    + In Canada STOCRIN(R) is marketed as SUSTIVA by BMS

    
    -----------------------
    (1) Markowitz M, Nguyen BY, Gotuzzo E, et al. Sustained antiretroviral
        efficacy of raltegravir as part of combination ART in treatment-naive
        HIV-1 infected patients: 96-week data. Te presented at the 17th
        International AIDS Conference; 5 August 2008; Mexico City.
    (2) ISENTRESS(TM) has been issued marketing authorization with
        conditions, pending the results of studies to verify its clinical
        benefit. Patients should be advised of the nature of this
        authorization.
    (3) Isentress product monograph.
    (4) Grinsztejn B, Nguyen BY, Katlama C, et al. Safety and Efficacy of the
        HIV-1 Integrase Inhibitor Raltegravir (MK-0518) in Treatment-
        Experienced Patients with Multidrug-Resistant Virus: A Phase II
        Randomised Controlled Trial. Lancet. 2007;369:1261-1269.
    (5) Hazuda DJ, Felock P, Witmer M, et al. Inhibitors of strand transfer
        that prevent integration and inhibit HIV-1 replication in cells.
        Science 2000; 287: 646-50.
    




For further information:

For further information: Julie Holroyde, HKDP Communications and Public
Affairs, (416) 413-4625, julie.holroyde@hillandknowlton.ca; Martine Drolet,
Merck Frosst Canada Ltd., Cell: (514) 833-6780, martine_drolet@merck.com


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