hepatitis C

The study showed a high rate of sustained virologic response in patients who received a four-drug regimen of daclastasvir, asunaprevir, PEG-interferon alfa and ribavirin.

Hope for Hepatitis C Patients

New combination of investigational drugs shows success

issue 15 | Spring 2012

A new combination of investigational drugs successfully suppressed hepatitis C genotype 1 infection in a high percentage of patients who had not responded to previous treatment, according to research led by a U-M hepatologist.

The work of Anna S. Lok, M.D., was published in January in the New England Journal of Medicine. The study focused on hepatitis C genotype 1, which is predominant in the United States and is the most difficult to treat.

In this pilot study, patients with hepatitis C genotype 1 infection who had not responded to previous treatment with PEG-interferon alfa and ribavirin were given a combination of two investigational direct-acting antiviral agents (daclatasvir and asunaprevir) alone, or were given these two antiviral agents along with PEG-interferon alfa-2a and ribavirin.

All the patients saw their hepatitis C viral load drop rapidly, says Lok, professor of Internal Medicine in the Division of Gastroenterology at the U-M Medical School and lead author of the study.

All 10 patients given the four-drug treatment — two direct-acting antiviral agents (daclastasvir and asunaprevir) that block the NS3 and NS5A regions of the hepatitis C virus, plus PEG-interferon alfa and ribavirin — had sustained virologic response with undetectable virus at the end of treatment and at 12 weeks after stopping treatment. Four of the 11 patients given only the two direct-acting antiviral agents also achieved sustained virologic response.

"The two recently approved hepatitis C drugs — telaprevir or boceprevir — combined with PEG-interferon alfa and ribavirin, have limited success in patients who have not responded to previous treatment with PEG-interferon alfa and ribavirin. There is a necessity for new combination regimens that can increase response rates in that population," says Lok, who also is director of Clinical Hepatology at U-M.

"The high rate of sustained virologic response in patients who received the four-drug regimen is very exciting. Although only four of 11 patients given the two direct-acting antiviral agents only achieved sustained virologic response, this is the first study to show that sustained virologic response can be achieved without the use of interferon or ribavirin. These data are very encouraging because PEG-interferon alfa and ribavirin are associated with many side effects and many patients with hepatitis C choose not to receive treatment for fear that they cannot tolerate those drugs."

The study was funded by Bristol-Myers Squibb.

"Overall, these results suggest that further research into combinations of direct-acting antiviral agents, with or without PEG-interferon and ribavirin, should be encouraged," Lok says.