Drug & Device Development

Adding telaprevir improves chronic hepatitis C therapy

Last Updated: 2011-09-07 14:11:09 -0400 (Reuters Health)

By C. Vidya Shankar MD

NEW YORK (Reuters Health) - Telaprevir added to standard therapy for chronic hepatitis C virus (HCV) was an improvement over the usual interferon/ribavirin protocol in a recent study in Japan.

Patients who received the first-generation HCV protease inhibitor telaprevir had a shorter duration of treatment, more rapid responses, and a higher rate of sustained virological response (SVR), the research team reports.

The telaprevir/interferon/ribavirin combination will "set the stage for a new standard of care for HCV," predicted Dr. Michael Manns from Medical School of Hanover, Germany. Dr. Mann, who sent his comments to Reuters Health by email, was not involved in the new study.

Pegylated interferon plus ribavirin -- the current standard of care -- achieves SVR only about half the time, lead author Dr. Hiromitsu Kumada from Toranomon University, Tokyo and colleagues pointed out in an August 8th online paper in the Journal of Hepatology.

For a randomized multicenter trial, the researchers enrolled 189 treatment-na�ve and otherwise healthy adults with HCV genotype-1. Each patient entered the study with a viral load of at least 5.0 log 10 IU/ml.

Two-thirds of the patients received telaprevir, interferon, and ribavirin for 12 weeks, followed by another 12 weeks of interferon and ribavirin. The remaining third received interferon and ribavirin for 48 weeks.

Patients in both groups received interferon 1.5 mcg/kg subcutaneously once a week, and everyone took ribavirin 200-600 mg twice a day. Patients in the telaprevir group took 750 mg three times a day.

Ribavirin and interferon doses were adjusted based on hemoglobin levels (ribavirin) or leukocyte, neutrophil, or platelet counts (interferon). Telaprevir dosing couldn't be changed; if hemoglobin fell below 8.5 mg/dL, triple therapy was stopped. If hemoglobin returned to at least 8.5 mg/dL within two weeks, treatment resumed but just with interferon and ribavirin.

Follow-up continued for 24 weeks after the end of therapy.

The patterns of HCV change in the two groups were very different, the research team said.

In the telaprevir group, the virus disappeared more often (98.4% vs. 79.4%, p<0.001) and more quickly (within 8 vs. 38 weeks).

With telaprevir, "the loss of HCV RNA increased constantly, sharply and swiftly," the authors wrote. Without telaprevir, "it gradually increased during the first 24 weeks on treatment."

The rates of rapid virological response (i.e., undetectable HCV RNA after four weeks of treatment) with and without telaprevir were 84% vs. 4.8% (p<0.0001). Rates of sustained virological response were 73% vs. 49.2% with and without telaprevir (p=0.002).

In the telaprevir group, however, the total ribavirin dose was only 47.0% of the target, while it was 77.7% in the control group.

The triple therapy group also had more adverse reactions, including severe anemia (11.1% vs. 0%) and skin rashes of severity grade 3-4 (11.9% vs. 4.8%) -- although rates of treatment discontinuation for adverse reactions were similar between the groups.

"Although the triple therapy with telaprevir-based regimen for 24 weeks resulted in more adverse events and less total ribavirin dose than pegylated-interferon and ribavirin for 48 weeks, it was able to achieve higher (rates of) sustained viral response within (a) shorter duration" with careful monitoring of adverse events and modifying the ribavirin dose as required, the researchers concluded.

Dr. Manns told Reuters Health in his email that he expects the telaprevir combination to have a role in treatment-na�ve hepatitis C, relapsed patients, and partial responders.

"Alternatives are boceprevir and the drugs under development, so called second wave HCV protease inhibitors, HCV polymerase inhibitors and maybe cyclophilin A inhibitors," he added.

The U.S. Food and Drug Administration approved telaprevir (Incivek; Vertex Pharmaceuticals) this past May. In July, a European Medicines Agency statement said its Committee for Medicinal Products for Human Use had recommended the granting of a marketing authorization for telaprevir (Incivo; Janssen-Cilag International).

SOURCE: http://bit.ly/ofORGg

J Hepatol 2011.