The drug telaprevir (Incivek) offers a marked improvement in the treatment of most common form of hepatitis C infection, according to an international team of researchers led by Dr. Ira M. Jacobson, NewYork-Presbyterian Hospital / Weill Cornell Medical Center.
Their study, published an edition of the New England Journal of Medicine, led to the approval of the agent for patient use by the U.S. Food and Drug Administration on May 23.
The ADVANCE results showed that telaprevir in combination with standard therapy (pegylated interferon and ribavirin) cure the virus in 75 percent of treated patients compared with 44 percent of patients receiving standard therapy alone.
In addition, about 60 percent of patients treated with telaprevir had undetectable virus at weeks 4 and 12 of treatment, and who were eligible under the terms of the study to receive 24 weeks of total treatment – half the standard time required for treatment – about 90 percent healed.
Telaprevir represents a “quantum leap forward into a new era for hepatitis C,” says Dr. Jacobson, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Professor and Distinguished Medicine New York-Presbyterian Hospital / Weill Cornell Medical Center. “This agent goes directly to the virus, along with the also recently introduced protease inhibitor boceprevir, is the first of a coming wave of new treatments to help the medical community to eradicate hepatitis C infection in most patients. ”
Over 3 million people in the United States have chronic hepatitis C virus (HCV). The infection, usually transmitted by blood, he moved to the liver, which is mounted a chronic immune response in an attempt to clear. This persistent inflammation can lead to liver damage, cirrhosis or organ failure. Treatment to eradicate the virus often fail, leaving patients with few options other than a liver transplant.
Dr. Jacobson believes that adoption of telaprevir to be a breakthrough in the search for more than two decades to HCV treatment more effective. Multicenter study was part of the first interferon therapy, which stimulates the body’s defenses against HCV, and also participated in the studies that established that the addition of pegylated interferon ribavirin is beneficial, and initial studies demonstrate the effectiveness interferon itself. In 1999, he helped create the Center for the Study of Hepatitis C and serves as medical director of the Center. A joint program of Rockefeller University and Cornell NewYork-Presbyterian/Weill, the Center is a comprehensive, multidisciplinary center dedicated to the study of hepatitis C and liver disease.
Telaprevir is similar in concept to the drugs used to treat HIV. It is a protease inhibitor that closes the enzyme that processes the protein product of the viral genome of HCV after infecting human cells. The drug is effective against HCV genotype 1, which is responsible for nearly three-quarters of all hepatitis C infections in the United States and is also the predominant genotype in Europe, Japan and other countries.
In the ADVANCE study clinic that 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 in combination with standard therapy for 8 or 12 weeks followed by standard therapy with a total duration of treatment 24 or 48 weeks. The researchers found that sustained virological response occurred in patients receiving more than 12 weeks (75 percent) or 8 weeks (69 percent) of telaprevir with standard therapy alone (44 percent). (NOTE: Drug package insert reflects the increase in SVR rates of 79 percent, 72 percent and 46 percent, respectively, derived from analysis of review). In total, 58 percent of patients treated with telaprevir received 24 weeks of total treatment.
There were substantial benefits of telaprevir in subgroups of patients who do not generally respond well to standard treatment, Dr. Jacobson says. For example, 62 percent of African Americans participating patients achieved viral cure with 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 patients similar to standard therapy. “We have closed the gap in the healing of 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 PROVE2 the European study, both studies were published on April 30, 2009 at the New England Journal of Medicine.
Dr. Jacobson noted that the use of telaprevir is added to the side effects of standard therapy, but the marked increase in the effectiveness of these side effects is greater, adding that the risk-benefit ratio is favorable for telaprevir.
“Telaprevir is not the end of the story. There are many medications that evaluates exciting,” he says. “Our goal is to cure most precious of HCV in patients with a cocktail of drugs fast-acting and well tolerated with a direct action against the virus or, in some cases can reach the host factors that contribute to replication HCV or liver disease as a result. Many lives were saved. ”
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 financial support from Vertex, Roche (manufacturer of peginterferon and ribavirin), Schering-Plough (manufacturer of peginterferon and ribavirin).
This article was first published by NewYork-Presbyterian Hospital / Weill Cornell Medical Center / Weill Cornell Medical College.