Telaprevir ( Incivek ) provides a improvement in the treatment of the most common form of hepatitis C infection. A study, carried out by researchers at Presbyterian/Weill Cornell in New York and published in of the New England Journal of Medicine ( NEJM ), led to approval of the agent for patient use by the FDA ( Food and Drug Administration ).

Results of the ADVANCE trial showed that Telaprevir combined with standard therapy ( Pegylated-Interferon and Ribavirin ) cured the virus in 75% of patients treated compared with 44% of patients who received standard therapy alone.

Furthermore, of the nearly 60% 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% were cured.

Telaprevir 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.

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% ) or 8 weeks ( 69% ) of Telaprevir than with standard therapy alone ( 44% ).
In all, 58% 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. For example, 62% of participating African-American patients achieved a viral cure with the Telaprevir-based regimen, compared with 25% of African-Americans treated with standard therapy.
In addition, 62% of patients with advanced liver cirrhosis achieved a viral cure with Telaprevir compared with 33% of similar patients on standard therapy.

The results confirm the findings of the U.S. Phase 2 PROVE1 study and the European PROVE2 study.

Source: Presbyterian Hospital / Weill Cornell Medical Center / Weill Cornell Medical College, 2011

XagenaMedicine2011