Isentress (raltegravir), in Combination with Optimized Background Therapy (OBT), Provided Sustained Viral Suppression in Highly Treatment-Experienced Patients Infected with HIV, through 48 WeeksCHICAGO--(BUSINESS WIRE)--Sep 18, 2007 - Results from an on-going Phase II study showed that antiretroviral suppression was sustained after 48-weeks of treatment with ISENTRESS(TM) (raltegravir), an investigational oral integrase inhibitor, in combination with optimized background therapy (OBT) versus placebo plus OBT in treatment-experienced HIV-infected patients failing therapy and who had virus resistant to three classes of oral antiretroviral drugs. The results from this ongoing Phase II study also showed that ISENTRESS dosed at 200 mg, 400 mg, 600 mg orally twice daily in combination with OBT was generally well tolerated in these patients (n=133).
ISENTRESS is under development by Merck & Co., Inc., Whitehouse Station, N.J. These results were presented today at the American Society for Microbiology's 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
"The findings at 48 weeks are consistent with the 24 week results and what we know to date about the drug's efficacy and tolerability profile," said Jose M. Gatell, M.D., Ph.D., senior consultant and head, Infectious Diseases and AIDS Units, Clinical Institute of Medicine and Dermatology; hospital clinic professor of medicine, University of Barcelona, Spain. "These results reinforce the drug's potential as the first in a promising new class of antiretroviral agents."
The FDA accepted a New Drug Application (NDA) for ISENTRESS (400 mg dosed twice daily) and has granted priority review status, a designation for investigational products that address unmet medical needs. Under the priority review designation, the FDA is expected to review and act on the NDA for ISENTRESS within six months of submission. Merck anticipates FDA action by mid-October and as planned is also moving forward with regulatory filings in countries outside of the United States.
ISENTRESS works to inhibit the insertion of HIV DNA into human DNA by the viral integrase enzyme. Inhibiting integrase from performing this essential function blocks the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV replication process - protease and reverse transcriptase - but currently no approved drugs that inhibit integrase. ISENTRESS is taken twice daily as a single tablet that is administered orally without regard to food and does not require boosting with ritonavir.
This multi-center, randomized, double-blind, dose-ranging, placebo-controlled study compared ISENTRESS plus OBT to placebo plus OBT in terms of reduction in HIV viral load, improvement in CD4 cell count and evaluation of safety and tolerability. Patients received ISENTRESS 200 mg, 400 mg, 600 mg or placebo, each dosed orally twice daily in combination with OBT. OBT was selected based on patients' prior treatment history and results from HIV resistance testing. Patients who entered the study were infected with HIV that was resistant to one or more drugs in each of the three oral anti-retroviral drug classes (nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PI)), were receiving anti-retroviral therapy (ART) for more than three months and had HIV viral loads greater than 5,000 copies/mL and CD4 counts greater than 50 cells/mm3.
When 400mg twice daily was selected as the phase III dose, the protocol was amended to allow all patients to receive open-label ISENTRESS 400 mg twice daily, after having reached at least week 24, the primary endpoint of the study. Patients with virologic failure after at least 16 weeks of double-blind therapy could enter an open-label post-virologic failure ISENTRESS arm.
The median duration of the double-blind period was approximately 40 weeks. Between week 24 and 48, 100 patients (including the six who still remained on placebo plus OBT) were switched to open-label ISENTRESS 400 mg twice daily plus OBT. By Week 48, greater than 85 percent of patients were receiving open label ISENTRESS or discontinued randomized therapy.
Results show that reductions in viral load observed at week 24 in the study were sustained over 48 weeks. After 48 weeks of therapy, 64 to 71 percent of patients receiving ISENTRESS at the doses studied plus OBT achieved viral load reductions below 400 copies/mL and 46 to 64 percent of patients receiving ISENTRESS plus OBT achieved viral load reduction to below 50 copies/mL. Increases in CD4 cell counts from baseline were 64 to 110 cells/mm3 for patients receiving ISENTRESS.
The regimen of ISENTRESS (at all doses studied) plus OBT was generally well tolerated and comparable to the tolerability of placebo plus OBT. The most commonly reported study therapy-related side effects (occurring in at least five percent of patients in at least one treatment group) were diarrhea, nausea, fatigue, vomiting, headache, and itching. Five patients discontinued treatment due to adverse experiences.
Expanded access program
ISENTRESS is currently available to qualified patients through an expanded access clinical research program, EARMRK. The global program provides early access to ISENTRESS as part of an optimized regimen for patients with HIV resistant to existing classes of antiretroviral medications Currently, more than 5,000 patients worldwide are participating in the expanded access program with ISENTRESS. Information about the program can be found at www.benchmrk.com
Prevalence of HIV/AIDS
In 2006, 1.1 million Americans were living with HIV and it is estimated that approximately 40,000 new cases of HIV/AIDS were diagnosed in the U.S.(i) Worldwide, an estimated 40 million people are infected with HIV/AIDS , and more than four million new infections occurred in 2006.(ii) AIDS is one of the top causes of infectious disease-related mortality worldwide, responsible for nearly three million deaths last year alone.(iii)
Merck HIV research
Merck's efforts to develop investigational treatments and a vaccine against HIV/AIDS have been under way for almost 20 years and continue today. Merck began its HIV integrase inhibitor research in 1993, and Merck was the first to demonstrate inhibition of HIV integrase in vitro and in vivo.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs.
The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.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 risk factors and cautionary statements in Item 1A 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) is a trademark of Merck & Co., Inc.
(i) CDC HIV/AIDS Fact Sheet "A Glance at the HIV/AIDS Epidemic," June 2007
(ii) UNAIDS, 2006 Report on the Global AIDS Epidemic
(iii) UNAIDS and WHO. AIDS Epidemic Update. December 2006.
Merck & Co., Inc.
Amy Rose, 908-423-6537
Lynn Kenney, 908-423-4188
Graeme Bell, 908-423-5185
Posted: September 2007