Thursday, March 29, 2012

MK-5172 : Next-Generation HCV Protease Inhibitor Shows Promise

This coverage is not sanctioned by, nor a part of, the International Association of Physicians in AIDS Care.

Medscape Medical News from the:
International Conference on Viral Hepatitis (ICVH) 2012
March 26 - 27, 2012; New York, New York

Next-Generation HCV Protease Inhibitor Shows Promise
Megan Brooks

March 28, 2012 (New York, New York) — In vitro data on a next-generation hepatitis C virus (HCV) NS3/4A protease inhibitor garnered considerable interest here at the International Conference on Viral Hepatitis 2012.

MK-5172, being developed by Merck & Co, demonstrated "potent activity" against the majority of primary first-generation protease inhibitor resistance-associated variants (RAVs) in biochemical and cell-based phenotype assays, reported Richard J. Barnard, PhD, from Merck & Co.

MK-5172 also inhibited patient-derived NS3 proteases across HCV genotypes and retained activity against HCV proteases isolated from 5 patients with vaniprevir RAVs.

In his presentation, Dr. Barnard noted that virologic failure with first-generation protease inhibitors is often associated with the emergence of RAVs; it is important that next-generation molecules are pangenotypic and active against first-generation protease inhibitor RAVs. "MK-5172 fulfills the profile expected of a next-generation" HCV protease inhibitor, he said.

Douglas T. Dieterich, MD, professor of medicine from the division of liver diseases at Mount Sinai School of Medicine in New York City, who was not involved in the study, told Medscape Medical News that "MK-5172 represents a promising potential best-in-class second-generation protease inhibitor."

"MK-5172 is a truly second-generation protease inhibitor," he explained. "This is really good news for the people who have already failed treatment with a first-generation protease inhibitor."

MK-5172, Dr. Dieterich said, "has activity against the most common resistance mutations caused by telaprevir and boceprevir. Even more encouraging for global use, it is active against genotypes 1, 2, 4, 5, and 6."

Dr. Barnard reports being an employee of Merck & Co and owning stock in the company. Dr. Dieterich reports financial relationships with Bristol-Myers Squibb, Gilead Sciences, Roche Laboratories, and Boehringer Ingelheim. 

International Conference on Viral Hepatitis (ICVH) 2012: Oral Abstract: 79340. Presented March 26, 2012.

Megan BrooksMegan Brooks is a freelance writer for Medscape.

Disclosure: Megan Brooks has disclosed no relevant financial relationships.

Related Audio - Oral Abstract: Breakthroughs in Hepatitis
Click Here To Listen
Tuesday, March 06, 2012 9:36 PM

CROI 2012 Seattle - 19th Conference on Retroviruses and Opportunistic Infections: Oral Abstract Sessions

"Moderator" by Juan Berenguer of Hosp Gregorio Maranon, Madrid, Spain
"Moderator" by Sanjay Bhagani of Royal Free Hosp, London, UK

"Tipranavir in Combination with Pegylated Interferon-α-2a+Ribavirin in HCV/HIV-co-infected Patients:  A 24-Week Treatment Interim Analysis" by Douglas Dieterich of Mt Sinai Sch of Med, New York, NY, US

"Boceprevir+Pegylated Interferon+Ribavirin for the Treatment of HCV/HIV-co-infected Patients: End of Treatment (Week 48) Interim Results" by Mark Sulkowski of Johns Hopkins Univ Sch of Med, Baltimore, MD, US

"Evaluation of NS3 Amino Acid Variants in a Phase 1b Study of GT1 Infection with the HCV Protease Inhibitor, MK-5172" by Richard Barnard of Merck & Co, Inc, Whitehouse Station, NJ, US

"The Pharmacokinetic Interactions of HCV Protease Inhibitor TMC435 with Rilpivirine, Tenofovir Disoproxil Fumarate, Efavirenz, or Raltegravir in Healthy Volunteers" by Sivi Ouwerkerk-Mahadevan of Tibotec BVBA, Beerse, Belgium

"Ribavirin Is Needed in Addition to Pegylated Interferon for Optimal Treatment Responses in the Treatment of Acute HCV Genotype 2 and 3 Infection in HIV-co-infected Individuals" by Christoph Boesecke of Univ Hosp Bonn, Germany

"Distinct Motifs in the HCV Poly-U/UC RNA Domain Are Recognized by RIG-I and Trigger Innate Immune Signaling and Governance of HCV/HIV Co-infection" by Gretja Schnell of Univ of Washington, Seattle, US

"Genome-wide Study of Spontaneous Resolution of HCV Infection" by David Thomas of Hepatitis C Spontaneous Resolution Study Consortium, Johns Hopkins Univ, Baltimore, MD, US

"Tenofovir Treatment for =8 Years Results in Pronounced HBsAg Decline in HBeAg+ HIV/HBV-co-infected Patients" by Theodora de Vries-Sluijs of Erasmus Med Ctr, Rotterdam, The Netherlands

"100% Rapid Virologic Response for PSI-7977 + Ribavirin in Genotype 1 Null Responders
(ELECTRON): Early Viral Decline Similar to that Observed in Genotype 1 and Genotype 2/3 Treatment-naïve Patients" by Edward Gane of Auckland City Hosp, New Zealand

View Abstract- CME
International Conference on Viral Hepatitis 2012
MK-5172, a Next Generation HCV NS3/4A Protease Inhibitor is Active against Common Resistance-Associated Variants (RAVs) and Exhibits Cross-Genotype Activity

No comments:

Post a Comment