(photo credit: Courtesy)
NEW YORK - 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
Their study, published an edition of the
New England Journal of Medicine, led to approval of the agent for
patient use by the US Food and Drug Administration on May 23.
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.
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
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
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.
results confirm the findings of the US 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
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
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).This article was first published by NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College.