Results of an Initial Phase II Study Showed That MK-0518, an Investigational Integrase Inhibitor, Provided Superior Reduction in HIV Viral RNA Vs. Placebo in Treatment-Naive HIV-Infected Patients

Merck & Co., Inc. In a 10-day monotherapy trial, patients taking MK-0518 achieved a 98 percent reduction in HIV-RNA across all dosages tested, and at least half achieved HIV-RNA copies of 400 per mL or less

Initial phase ll clinical trial results presented at the European AIDS Clinical Society meeting today showed that the investigational HIV-1 integrase inhibitor MK-0518 tablet had potent reduction in viral load over a 10-day course as monotherapy. Significant viral load reduction (p=0.001) versus placebo was shown across all doses studied in previously untreated HIV-infected patients (n=28), according to study authors. CD4 count was not significantly different from baseline.

MK-0518, developed by Merck & Co, Inc., Whitehouse Station, New Jersey, USA, could be the first in a new class of investigational anti-retroviral therapy (ART) called integrase inhibitors that may inhibit the integrase enzyme from inserting HIV viral DNA into the human gene*. Inhibiting integrase from performing this essential function blocks the ability of the virus to replicate and infect new cells.

“This study further demonstrated proof-of-concept for the antiviral activity of HIV integrase inhibitors as a new and exciting class of anti-retroviral agents,” said Robin Isaacs, MD, Executive Director, Infectious Disease and HIV Vaccine Clinical Research, MSD. “MK-0518 was generally well tolerated and demonstrated potent short-term viral load reduction as monotherapy in this small, early trial.”

In the multi-center, double-blinded, randomized trial, 35 ART-naive (previously untreated) patients were given one of four doses of MK-0518 as monotherapy (100 mg, 200 mg, 400 mg, 600 mg) or placebo twice daily for 10 days. Patients at baseline (MK0518: 28, placebo: 7) had HIV-RNA of at least 5000 copies/mL and CD4 counts of at least 100 cells/uL. Primary endpoints of the study were the safety and tolerability profiles of MK-0518 and the reduction from baseline in HIV-RNA. Patients undergoing immunosuppressive therapy or with diagnosed acute hepatitis, chronic liver disease or renal disease were excluded from the trial(1).

Results demonstrated a 1.7 to 2.2 log10 copies/mL reduction in HIV-RNA across all MK-0518 treatment groups (a decline of 98 percent from baseline) and a 0.2 log10 copies/mL reduction for placebo (p(less than)0.001). In addition, at least 50 percent of patients in each MK-0518 group achieved an HIV-RNA of (less than) 400 copies/mL by Day 10(1).

MK-0518 therapy was generally well tolerated. The most common adverse experiences (AEs) were headache, fatigue and dizziness; these were similar between the MK-0518 and the placebo groups. There were no discontinuations due to AEs and no serious AEs(1).

Based on these results, a 48-week dose-ranging trial of MK-0518 versus efavirenz – a non-nucleoside reverse transcriptase inhibitor – in combination therapy has been initiated in treatment-naive patients. Additional studies are necessary to evaluate the efficacy and safety profile of this investigational drug over a longer period of time and in a larger number of patients.

HIV resistance to drugs increases

It is estimated that up to 78 percent of patients treated with anti-retroviral drugs have developed resistance to more than one therapeutic class of these medicines. The problem of resistance also has increased substantially in drug-naive patients. The proportion of treatment-naive patients who carried resistant virus has grown to more than 20 percent today from eight percent in 1999(2).

Despite the availability of drugs to treat HIV/AIDS, the epidemic continues. An estimated 40 million people are currently infected worldwide. AIDS is now the largest infectious disease cause of mortality worldwide, responsible for three million deaths each year(2).

Merck’s leadership in developing breakthrough treatments and a vaccine against HIV/AIDS has been underway for more than 15 years and continues today. Merck was the first to elucidate integrase strand transfer inhibition and to define the mechanism of action. Merck was also the first to demonstrate the mechanism of action in vitro and in vivo.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in more than 20 therapeutic categories. 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.

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 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, 2004, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

*Inside the host cell, the virus turns its RNA into DNA with another enzyme, reverse transcriptase. Integrase is one of three HIV enzymes required by the virus to reproduce.

(1) Morales-Ramirez JO, Teppler H, Kovacs C, Steigbigel RT, Cooper D, Liporace RL, Schwartz R, Wenning L, Zhao J, Gilde L, Isaacs R, Nguyen B-Y; Antiretroviral Effect of MK-0518, a Novel HIV-1 Integrase Inhibitor, in ART-Naive HIV-infected Patients. EACS presentation, Dublin, Ireland, November 2005.

(2) Data available on file, MSD.