All-oral Drug Combination Delivers High Hepatitis C Cure Rates

An all-oral antiviral drug combination that included ombitasvir and dasabuvir with and without ribavirin resulted in high cure rates among patients with hepatitis C virus infections in first-time treatments for the disease, according to an article published in the May 4, 2014, issue of the New England Journal of Medicine.

Treatment groups in 2 studies had sustained virologic response (SVR) rates that were superior to the historical response rate with a peginterferon-containing telaprevir-based regimen, according Peter Ferenci, MD, and David Bernstein, MD, lead authors of the article. SVR indicates there is no detectable level of the hepatitis C virus (HCV) in the blood stream and is likened to a cure of the disease.

“These findings suggest that in previously untreated patients with HCV infection and no cirrhosis, this 12-week regimen of 3 direct-acting antiviral agents is efficacious both with and without ribavirin,” Ferenci and Bernstein wrote.

The authors pointed out that ribavirin has been an important component in more traditional HCV treatment of peginterferon therapy with first generation protease inhibitors but noted that trial data suggest it may not always be needed with newer, interferon-free regimens of direct-acting antiviral agents.

After 12 weeks of treatment, the rate of SVR ranged from 90.2% to 99.5% among patients in 2 phase 3 double-blind randomized studies who received 3 direct-acting antiviral agents ABT-450/r, ombitasvir, and dasabuvir with or without ribavirin. The patients were either HCV genotype 1a or 1b, did not have cirrhosis, and had not previously been treated for the virus.

HCV genotype 1 is the most common HCV infection and includes sub-genotypes 1a and 1b. Chronic infection of the virus can cause severe liver damage, including cirrhosis, liver cancer, and the need for a liver transplant.

ABT-450r is a ritonavir-boosted protease inhibitor administered to increase ABT-450 plasma levels and half-life that enables once-daily dosing. Ombitasvir is a NS5A inhibitor and dasabuvir is a nonnucleoside NS5B polymerase inhibitor.

There were 419 patients who received drug in the HCV genotype 1b cohort and 305 patients in the genotype 1a cohort. Patients in both groups were given 12 weeks of ABT-450/r-ombitasvir (which included a daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), 250 mg of dasabuvir twice daily, and either ribavirin administered in a dose according to body weight or matching placebo.

The primary endpoint for both studies was an SVR 12 weeks after end of treatment. Patients with HCV genotype 1b infection had higher SVR (99.5% with ribavirin and 99.0% without), than patients with HCV genotype 1a (97.0% with ribavirin and 90.2% without).

Virologic failure rate was higher among patients with genotype 1a infection who did not receive ribavirin (7.8% vs 2.0%). In the genotype 1b infection group, one patient had virologic failure and data was unavailable for 2 patients 12 weeks after treatment.

Two patients dropped out of study participation due to adverse events. The most common adverse events were fatigue, headache, and nausea.

The studies, identified as PEARL-III and PEARL-IV, were funded by AbbVie.