Healthcare Industry News:  antiviral 

Biopharmaceuticals HIV/AIDS

 News Release - October 2, 2006

Viral Suppression in Triple-Class Drug Resistant Patients Maintained after 24 Weeks of Treatment with MK-0518, an Investigational HIV Integrase Inhibitor, Plus Optimized Background Therapy (OBT)

Tolerability of MK-0518 Plus OBT Was Comparable to Placebo Plus OBT

SAN FRANCISCO--(HSMN NewsFeed)--Greater antiretroviral suppression was maintained after 24 weeks of therapy with MK-0518(i), an investigational oral HIV integrase inhibitor in combination with optimized background therapy (OBT) versus placebo plus OBT in HIV-infected patients who failed antiretroviral therapy (ART) and who were resistant to drugs in all three classes of oral antiretroviral drugs. The interim results from this ongoing Phase II study also showed that MK-0518 dosed at 200 mg, 400 mg, 600 mg orally twice daily in combination with OBT was generally well tolerated in these patients (n=179).

MK-0518 is under development by Merck & Co., Inc., Whitehouse Station, N.J.

These results were presented as a late breaker today at the American Society for Microbiology's 46th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

"These findings are very encouraging, especially since the results observed at week 16 that were reported earlier this year at CROI(ii) are sustained out to week 24," said lead study author Beatriz Grinsztejn M.D., Ph.D., head of the infectious disease service - IPEC/Fiocruz and director of the HIV/AIDS Clinical Trials UNIT, Evandro Chagas Clinical Research Institute - Oswaldo Cruz Foundation, Rio De Janeiro, Brazil. "In this presentation and the previous one at CROI 2006, MK-0518 when used in combination with OBT in patients with advanced HIV infection significantly reduced HIV viral load when compared to placebo plus OBT. All doses of MK-0518 were generally well tolerated."

About MK-0518

MK-0518 belongs to a new class of investigational antiretroviral agents called integrase inhibitors that inhibit the insertion of the HIV viral DNA into human DNA. 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 the other two enzymes - protease and reverse transcriptase - but there are no approved drugs that inhibit integrase.

Study design

This multi-center, randomized, double-blind, dose-ranging, placebo-controlled study compared MK-0518 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 MK-0518 200 mg, 400 mg, 600 mg or placebo, each dosed orally twice daily in combination with OBT. Optimized background therapy 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 antiretroviral drug classes (nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PI)), were receiving 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.

Study results

Interim results from 178 patients, after 24 weeks of treatment, showed that 57 to 67 percent of patients taking MK-0518 in combination with OBT achieved HIV RNA viral load reduction below 50 copies/mL across all doses (200 mg, 400 mg, and 600 mg) versus only 14 percent of patients taking placebo plus OBT. In addition, 70 to 73 percent of patients taking MK-0518 in combination with OBT achieved HIV RNA viral load reduction below 400 copies/mL for all doses studied (200 mg, 400 mg, 600 mg) versus only 16 percent of patients taking placebo plus OBT.

The median duration for prior use of ARTs was approximately nine years for all groups, mean baseline HIV viral load ranged from 4.6 to 4.8 log10 copies/mL and mean baseline CD4 cell counts ranged from 220 to 274 cells/mm3.

The regimen of MK-0518 (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, headache and itching. Four patients discontinued treatment due to adverse experiences.

HIV resistance to drugs increases

It is estimated that up to 78 percent of patients who fail antiretroviral therapy have developed resistance to more than one therapeutic class of these medicines. In addition, increasing drug resistance has been noted even in drug-naive individuals. The proportion of treatment-naive patients who carry resistant virus has grown to more than 20 percent today from eight percent in 1999.

Despite the availability of drugs to treat HIV/AIDS, the epidemic continues. An estimated 40 million people are currently infected worldwide, and it is estimated that more than four million new infections occur worldwide annually. AIDS is one of the top causes of infectious disease-related mortality worldwide, responsible for approximately three million deaths each year.

Merck's efforts to develop investigational treatments and a vaccine against HIV/AIDS have been underway for almost 20 years and continue today. Merck began its HIV integrase inhibitor research in the early 1990's, and Merck was the first to demonstrate integrase strand transfer inhibition and to define the mechanism of action. Merck was also the first to demonstrate HIV integrase inhibitor's antiviral inhibition 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 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.

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, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

MK-0518 is an investigational oral HIV integrase inhibitor under development by Merck & Co., Inc.

(i)MK-0518 is compatible with all ARTs and in preclinical evaluation was determined to have no genotoxicity in vitro or in vivo, is not a potent inhibitor or inducer of CYP3A4 (does not require ritonavir boosting) and is predominantly metabolized via glucuronidation (UGT1A1).

(ii)Grinsztejn et al, CROI 2006, Abstract 159LB


Source: Merck

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