Breakthrough in Treatment of Hepatitis C

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http://www.sciencedaily.com/releases/2011/06/110622224510.htm

Breakthrough in Treatment of Hepatitis C

ScienceDaily (June 22, 2011) — The drug telaprevir (Incivek) provides a dramatic

improvement in the treatment of the most common form of hepatitis C infection,

says an international team of investigators led by Dr. Ira M. son of

NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Their study, published in the June 22 edition of the New England Journal of

Medicine, led to approval of the agent for patient use by the U.S. Food and Drug

Administration on May 23.

Results of the ADVANCE trial showed that telaprevir combined with standard

therapy (pegylated-interferon and ribavirin) cured the virus in 75 percent of

patients treated compared with 44 percent of patients who received standard

therapy alone.

Furthermore, of the nearly 60 percent of telaprevir-treated patients who had

undetectable viral levels at weeks 4 and 12 of treatment, and who were eligible

by the terms of the study to receive 24 weeks of total treatment -- half the

time required for standard treatment -- approximately 90 percent were cured.

Telaprevir represents a " quantum leap forward into a new era of hepatitis C

therapy, " says Dr. son, chief of the Division of Gastroenterology and

Hepatology and the Astor Distinguished Professor of Medicine at

NewYork-Presbyterian Hospital/Weill Cornell Medical Center. " This agent directly

targets the virus and, together with the also recently introduced protease

inhibitor boceprevir, is the first of a coming wave of new treatments that will

help the medical community eradicate hepatitis C infection in a majority of

patients. "

More than 3 million people in the United States have chronic hepatitis C virus

(HCV) infection. The infection, which is usually transmitted by blood, settles

in the liver, which mounts a chronic immune response in an attempt to clear it.

This persistent inflammation can lead to liver damage, cirrhosis or failure of

the organ. Treatment to eradicate the virus often fails, leaving patients with

few options other than a liver transplant.

Dr. son considers the approval of telaprevir to be a major breakthrough in

the more than two-decade search for more effective HCV treatment. He was part of

the first multicenter study of interferon therapy that stimulates the body's

defenses against HCV, and he was also involved in studies that established that

the addition of ribavirin to pegylated-interferon was beneficial as well as the

initial studies demonstrating the effectiveness of interferon itself. In 1999,

he helped create the Center for the Study of Hepatitis C and serves as the

Center's medical director. A joint program of The Rockefeller University and

NewYork-Presbyterian/Weill Cornell, the Center is a comprehensive,

multidisciplinary center dedicated to the study of HCV and liver disease.

Telaprevir is similar in concept to drugs used to treat HIV. It is a protease

inhibitor that shuts down the enzyme that processes the protein product of the

viral genome after HCV infects human cells. The drug is effective against HCV

genotype 1, which is responsible for nearly three-fourths of all hepatitis C

infections in the United States and is also the predominant genotype in Europe,

Japan and elsewhere.

In the ADVANCE clinical trial of which Dr. son served as principal

investigator, 1,088 untreated patients diagnosed with HCV genotype 1 were

assigned to one of three treatment arms: standard therapy for 48 weeks, or

telaprevir combined with standard therapy for 8 or for 12 weeks, followed by

standard therapy alone for a total treatment duration of either 24 or 48 weeks.

The researchers found that sustained virologic response occurred in

significantly more patients receiving 12 weeks (75 percent) or 8 weeks (69

percent) of telaprevir than with standard therapy alone (44 percent). (Note: The

drug's package insert reflects higher SVR rates of 79 percent, 72 percent, and

46 percent, respectively, arising from revised analyses). In all, 58 percent of

telaprevir-treated patients received 24 weeks of total treatment.

There were substantial benefits of telaprevir in subgroups of patients who do

not generally respond well to standard therapy, Dr. son says. For example,

62 percent of participating African-American patients achieved a viral cure with

the telaprevir-based regimen, compared with 25 percent of African-Americans

treated with standard therapy. In addition, 62 percent of patients with advanced

liver cirrhosis achieved a viral cure with telaprevir compared with 33 percent

of similar patients on standard therapy. " We have closed the gap in cure in

these populations, " he says.

The results confirm the findings of the U.S. Phase 2 PROVE1 study, which was

co-authored by Dr. son, and the European PROVE2 study; both studies were

published April 30, 2009, in the New England Journal of Medicine.

Dr. son notes that telaprevir use does add to the side effects of standard

therapy, but the marked increment of efficacy outweighs these side effects,

adding that the risk-benefit ratio is very favorable for telaprevir.

" Telaprevir is not the end of the story. There are many exciting drugs being

evaluated, " he says. " Our most cherished goal is to cure HCV in all patients

with a cocktail of fast-acting and well-tolerated drugs that have direct action

against the virus or, in some cases, may target factors in the host that

contribute to HCV replication or its consequent liver disease. Many lives will

be saved. "

Telaprevir was developed by Vertex Pharmaceuticals Incorporated in collaboration

with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex provided

funding for the study. Dr. son has received consulting fees and/or grant

support from Vertex, Roche (maker of peginterferon and ribavirin) and

Schering-Plough (maker of peginterferon and ribavirin).

Co-authors include Dr. G. McHutchison and Dr. J. Muir from Duke

Clinical Research Institute and Division of Gastroenterology, Duke University

Medical Center, Durham, N.C.; Dr. Geoffrey Dusheiko, from Royal Free Hospital,

Centre for Hepatology, London, United Kingdom; Dr. M. Di Bisceglie from

Saint Louis University School of Medicine, Saint Louis, Mo.; Dr. K. Rajender

Reddy from the University of Pennsylvania, Division of Gastroenterology,

Philadelphia, Pa.; Dr. H. Bzowej from the California Pacific Medical

Center, San Francisco, Calif.; Dr. Marcellin from Hôpital Beaujon,

Service d'Hépatologie and INSERM CRB3, Clichy, France; Dr. Ferenci from

the University of Vienna, Vienna, Austria; Dr. Flisiak from Medical

University of Bialystok, Department of Infectious Diseases and Hepatology,

Bialystok, Poland; Dr. from Storr Liver Unit, Westmead Millennium

Institute for Medical Research and Westmead Hospital, University of Sydney,

Westmead, Australia; Dr. Rizzetto from the University of Turin, Department

of Gastroenterology, Turin, Italy; Dr. Shouval from Hadassah-Hebrew

University Hospital, Liver Unit, Jerusalem, Israel; Dr. Ricard Sola from

Hospital del Mar, IMIM, Universitat Autónoma de Barcelona, Barcelona, Spain; Dr.

A. Terg from Hospital de Gastroenterología Dr Bonorino Udaondo, Buenos

Aires, Argentina; Dr. M. Yoshida from the University of British Columbia

and Vancouver General Hospital, Vancouver, B.C., Canada; Dr. Nathalie Adda, Leif

Bengtsson, Dr. Abdul J. Sankoh, Dr. Tara L. Kieffer, Dr. and Dr.

S. Kauffman from Vertex Pharmaceuticals Incorporated, Cambridge, Mass.;

and Dr. Stefan Zeuzem from Johann Wolfgang Goethe University Medical Center,

Department of Internal Medicine, furt am Main, Germany, for the ADVANCE

Study Team.

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Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by New York- Presbyterian Hospital/Weill Cornell Medical

Center/Weill Cornell Medical College.

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Journal Reference:

1.Ira M. son, G. McHutchison, Geoffrey Dusheiko, M. Di

Bisceglie, K. Rajender Reddy, H. Bzowej, Marcellin, J.

Muir, Ferenci, Flisiak, , Rizzetto,

Shouval, Ricard Sola, A. Terg, M. Yoshida, Nathalie Adda, Leif

Bengtsson, Abdul J. Sankoh, Tara L. Kieffer, , S. Kauffman,

Stefan Zeuzem M.D. Telaprevir for Previously Untreated Chronic Hepatitis C Virus

Infection. New England Journal of Medicine, 2011; 364 (25): 2405 DOI:

10.1056/NEJMoa1012912