Study Showed Raltegravir Increased CD4 Cells More Than Efavirenz, with
Significantly Fewer Side Effects
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
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,
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
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. More information about Merck Frosst and
ISENTRESS(TM) is available at www.merckfrosst.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 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
(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) http://www.farha.qc.ca/en/html/sidaqc.html Last accessed
September 26, 2008.
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