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New Phase III Study in Previously Untreated HIV Patients Showed Raltegravir Reduced HIV Viral Load to Undetectable Levels, Comparable to Efavirenz, When Taken in Combination with Other Medicines

MONTREAL, Oct. 26 /CNW Telbec/ - In a new Phase III study that compared Merck's HIV integrase inhibitor raltegravir to efavirenz, raltegravir reduced HIV viral load to undetectable levels (less than 50 copies/mL) in 86 percent of patients (241 out of 280) compared to 82 percent of patients (230 out of 281) treated with efavirenz in previously untreated HIV patients. Both medicines were taken in combination with tenofovir/emtricitabine. Patients taking raltegravir had a greater increase in CD4 cell counts, an average increase of 189 cells/mm3, compared to patients taking efavirenz who had an average increase of 163 cells/mm3.

In addition, drug-related adverse events of any severity occurred in fewer patients (44 percent vs. 77 percent; p less than 0.001) treated with raltegravir. The use of raltegravir in treatment-naive patients is investigational. These findings were presented today at the late-breaker session of the joint 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46th Annual Meeting in Washington, D.C.

"This study showed that raltegravir in combination with other antiretrovirals effectively lowered the amount of virus in the blood to below detectable levels in 86 percent of treatment-naive patients, increased CD4 cell count and was better tolerated than the standard of care," said Dr. Fiona Smaill, Professor and Chair, Department of Pathology and Molecular Medicine and Co-Director, Special Immunology Services/HIV Clinic, McMaster University "These results are consistent with the efficacy and safety profile already established with raltegravir in treatment-experienced patients and demonstrate that raltegravir may become an important treatment option for previously untreated patients." Raltegravir is the first integrase inhibitor approved 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. The safety and efficacy of raltegravir have not been established in treatment-naive adult or paediatric patients.

Raltegravir studied in untreated HIV patients in Phase III trial

These findings presented today are from an ongoing multi-centre, double-blind, randomised, active-controlled Phase III trial of previously untreated HIV-infected patients called STARTMRK. In this study, 563 treatment-naive, HIV-infected patients received either 400 mg raltegravir administered orally twice daily in combination with tenofovir/emtricitabine or 600 mg efavirenz dosed orally once daily in combination with the same agents. The primary endpoints were reductions in HIV RNA to less than 50 copies/mL and an evaluation of safety and tolerability at week 48. Secondary endpoints included antiretroviral activity as measured by the proportion of patients achieving HIV RNA less than 400 copies/mL and change from baseline in CD4 cell counts at week 48. An additional secondary safety endpoint was the proportion of patients experiencing nervous system symptoms through week eight.

Suppression of viral load and increase in CD4 cell counts maintained through 48 weeks

At baseline, geometric mean HIV RNA levels for patients on the regimen including raltegravir 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 raltegravir and efavirenz, respectively. After 48 weeks of treatment, 86 percent of patients receiving the regimen with raltegravir achieved reductions in HIV RNA levels below 50 copies/mL. Results were comparable for patients taking the efavirenz regimen, with 82 percent of patients achieving reductions in HIV RNA levels below 50 copies/mL in the same time period. Similarly, 90 percent of patients receiving the regimen containing raltegravir maintained reductions in HIV RNA levels to below 400 copies/mL compared to 86 percent of patients taking the regimen containing efavirenz. Time to virologic response was significantly shorter for patients taking raltegravir compared to those taking the efavirenz regimen, confirming the rapid viral load reductions demonstrated by raltegravir in previous trials. At week eight, 74 percent of patients receiving the regimen with raltegravir achieved HIV RNA levels below 50 copies/mL compared to 38 percent of patients receiving the regimen with efavirenz. Patients receiving the regimen with raltegravir had greater immunologic response as measured by change from baseline in CD4 cell count. At week 48 the mean increase from baseline in CD4 cell count was 189 cells/mm3 for patients receiving raltegravir and 163 cells/mm3 for patients receiving efavirenz.

Tolerability profile of raltegravir in STARTMRK study

The most commonly reported adverse experiences in patients receiving raltegravir and efavirenz, respectively, were headache (3.9 percent versus 4.6 percent), nausea (2.8 percent versus 3.5 percent), dizziness (1.4 percent versus 6.4 percent), insomnia (3.6 percent versus 3.2 percent), diarrhoea (1.1 percent versus 2.8 percent) and fatigue (1.4 percent versus 2.8 percent). Central nervous system symptoms were reported significantly less frequently with the group receiving raltegravir compared to the group receiving efavirenz through week eight (20.3 percent versus 52.1 percent; p less than 0.001). Cancer occurred in one patient taking the regimen with raltegravir and nine patients taking the regimen with efavirenz. Researchers also assessed lipid levels based upon the profile observed with raltegravir and efavirenz in an earlier Phase II trial in a similar population. Results from the STARTMRK study showed that raltegravir had minimal effect on lipid levels. The mean changes from baseline at week 48 for raltegravir and efavirenz, respectively, were 10 mg/dL and 32.7 mg/dL (p=0.001) for total cholesterol; 5.9 mg/dL and 16.1 mg/dL (p=0.001) for LDL cholesterol; 4.2 mg/dL and 10.0 mg/dL (p=0.001) for HDL cholesterol; and -2.8 mg/dL and 37.4 mg/dL (p=0.001) for triglycerides. "These findings reinforce the efficacy and safety seen with raltegravir in Phase II trials in treatment-naive patients, and are consistent with efficacy already established in treatment-experienced patients for whom it is currently approved," said Dr. Michel Cimon, Medical Director, Merck Frosst Canada. "Viral load reductions and CD4 cell count increases were sustained through 48 weeks in this study."


ISENTRESS(TM) (raltegravir) was approved by Health Canada in November 2007 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. Raltegravir attacks the HIV virus in a way that is different to 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 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.(1)

<< About HIV-AIDS in Canada

- As of June 2007, 63,604 people in Canada have tested positive for HIV. Of these people, 83.2% are male and 16.8% are female.(2) - Of the estimated 58,000 people living with HIV/AIDS at the end of 2005 in Canada, approximately 27% were unaware of their HIV status.(3) - The number of new HIV infections in 2006 has not decreased and may have increased slightly compared to 2002.(4) - In Canada, 11 new people are infected with HIV every day.(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.

Merck's commitment to providing access to treatment

Merck is committed to ensuring access to our antiretroviral medicines (ARVs) through a differential pricing policy that provides our ARVs at dramatically lower prices-at which Merck does not profit-to people living in the world's least developed countries and those hardest hit by the pandemic, as defined by various United Nations indices. Also, Merck is committed to seeking additional ways to reduce the cost of its ARVs for people living in the world's poorest countries and those hardest hit by the pandemic, including through partnering with external manufacturers and suppliers to achieve incremental efficiencies and cost savings.

About Merck Frosst Canada Ltd.

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.

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.

(TM) Trademark of Merck & Co., Inc., used under license.

<< (1) ISENTRESS(TM) product monograph (2) Public Health Agency of Canada. HIV and AIDS in Canada; Selected Surveillance Report to June 30, 2007. (3) Public Health Agency of Canada. HIV/AIDS Epi Updates. November 2007 (4) Public Health Agency of Canada, HIV and AIDS in Canada; Surveillance Report to December 31, 2006 (5) Last accessed September 26, 2008.


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Posted: October 2008