NewYork-Presbyterian/Weill Cornell physician-scientist leads study reporting that FDA-approved telaprevir-based regimen acts faster and offers a stronger viral cure than standard treatment
NEW YORK (June 23, 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. Jacobson of NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Their study, published in today's 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. Jacobson, chief of the Division of Gastroenterology and Hepatology and the Vincent 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. Jacobson 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. Jacobson 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. Jacobson 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. Jacobson, and the European PROVE2 study; both studies were published April 30, 2009, in the New England Journal of Medicine.
Dr. Jacobson 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."
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Telaprevir was developed by Vertex Pharmaceuticals Incorporated in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex provided funding for the study. Dr. Jacobson 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. John G. McHutchison and Dr. Andrew 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. Adrian 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. Natalie H. Bzowej from the California Pacific Medical Center, San Francisco, Calif.; Dr. Patrick Marcellin from Hôpital Beaujon, Service d'Hépatologie and INSERM CRB3, Clichy, France; Dr. Peter Ferenci from the University of Vienna, Vienna, Austria; Dr. Robert Flisiak from Medical University of Bialystok, Department of Infectious Diseases and Hepatology, Bialystok, Poland; Dr. Jacob George from Storr Liver Unit, Westmead Millennium Institute for Medical Research and Westmead Hospital, University of Sydney, Westmead, Australia; Dr. Mario Rizzetto from the University of Turin, Department of Gastroenterology, Turin, Italy; Dr. Daniel 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. Ruben A. Terg from Hospital de Gastroenterología Dr Bonorino Udaondo, Buenos Aires, Argentina; Dr. Eric 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. Shelley George and Dr. Robert S. Kauffman from Vertex Pharmaceuticals Incorporated, Cambridge, Mass.; and Dr. Stefan Zeuzem from Johann Wolfgang Goethe University Medical Center, Department of Internal Medicine, Frankfurt am Main, Germany, for the ADVANCE Study Team.
For more information, patients may call (866) NYP-NEWS.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University.
NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances -- including the development of the Pap test for cervical cancer; the synthesis of penicillin; the first successful embryo-biopsy pregnancy and birth in the U.S.; the first clinical trial for gene therapy for Parkinson's disease; the first indication of bone marrow's critical role in tumor growth; and, most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient.
NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian/The Allen Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and weill.cornell.edu.
http://www.eurekalert.org/pub_releases/2011-06/nyph-nsn062211.php
New Drug Effectively Treats Hepatitis C
Adding Incivek to standard therapy also cut treatment time in half, researchers say
By Steven ReinbergHealthDay Reporter
WEDNESDAY, June 22 (HealthDay News) -- The recently approved drug Incivek, combined with two standard drugs, is highly effective at treating hepatitis C, a notoriously difficult-to-manage liver disease, two new studies show.
The drug works not only in patients just starting treatment, but in those who failed earlier treatment, the research found.
The hepatitis C virus can lurk in the body for years, causing liver damage, cirrhosis and even liver failure.
"This is a significant advance in the treatment of hepatitis C," said Dr. David Bernstein, chief of the division of gastroenterology, hepatology and nutrition at North Shore University Hospital in Manhasset N.Y., who was not involved in either study.
"We know that if we can get rid of the hepatitis C, we can prevent the progression of [liver] disease," he said. "This means we can prevent the progression of cirrhosis, we can prevent the development of cancer and also prevent the need for liver transplantation in a large number of people."
Incivek (telaprevir) was approved by the U.S. Food and Drug Administration in May and is the second drug in a class of drugs called protease inhibitors to be approved to fight hepatitis C. The other drug, called Victrelis (boceprevir), was also approved in May.
The standard treatment for hepatitis C has been a combination of two drugs, pegylated-interferon and ribavirin, which are given for a year. If protease inhibitors such as Incivek are added to the mix, the "viral cure" rate improves and the treatment time is reduced to six months, researchers found.
Both reports were published in the June 23 online edition of the New England Journal of Medicine.
In one study, a Phase 3 trial known as ADVANCE, patients were randomly assigned to either a placebo or the treatment in a double-blind study, which means that neither the patients nor the researchers know who's getting the drug and who's getting a sham treatment. This type of study is considered the gold standard for clinical research.
In the ADVANCE trial, 1,088 patients with hepatitis C who had never been treated for the condition were randomly assigned to standard therapy for 48 weeks, or telaprevir combined with standard therapy for eight or for 12 weeks, followed by standard therapy alone for a total treatment time of either 24 or 48 weeks.
The researchers found that 79 percent of those receiving Incivek for the longest period (24 weeks) had a "sustained response," which basically means their hepatitis C was contained. Among those receiving standard care, 44 percent had a sustained response, the researchers noted.
"We have entered a new era of therapy for hepatitis C, which enables us to cure many more patients than we could before," said lead researcher Dr. Ira M. Jacobson, from Weill Cornell Medical College in New York City.
Incivek needs to be given along with pegylated-interferon and ribavirin, Jacobson said. The researchers learned early on that Incivek alone reduces the level of the virus, but later the virus can become resistant to the drug, he said.
For the second study, called the REALIZE trial, 663 patients with hepatitis C who had failed standard therapy were divided into three groups. One group received Incivek plus standard therapy, another group was started on pegylated-interferon and ribavirin and then had Incivek added. The third group received standard therapy alone.
Here, the researchers found up to an 88 percent sustained response in patients receiving Incivek, compared with a 24 percent sustained response in the standard treatment group.
"These drugs represent a real milestone in the treatment of this disease," said lead researcher Dr. Stefan Zeuzem, a professor of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.
"There were very limited treatment options in the past, but now many patients have excellent chances to be cured, even if they already have advanced disease," he said.
Bernstein noted that in the past, these patients could only be treated with more of the standard therapy for a longer period and the "cure" rate was only 10 percent. "Now you can treat these patients for six months with cure rates approaching 90 percent," he said. "You are really offering hope to a large number of patients."
The side effects of the medications include skin rashes, anemia, fatigue, itching, nausea, diarrhea, vomiting and taste changes. Some side effects were serious enough to cause a few participants to drop out, according to the study.
Incivek, made by Vertex Pharmaceuticals Inc., is sold to wholesalers for $49,200 for a four-week course of treatment, said Vertex spokeswomen Nikki Levy.
While both Incivek and Victrelis are important breakthroughs in the treatment of hepatitis C, new drugs with even fewer side effects and perhaps shorter treatment times are in clinical trials, Bernstein said.
Hepatitis C affects almost 4 million Americans, most of whom don't know they're infected. Often there are no symptoms, but it is the leading cause of liver transplantation in the United States and is linked to as many as 12,000 deaths a year, the researchers say.
More information
For more on hepatitis C, visit the U.S. U.S. National Institutes of Health.
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