An All-Oral Ribavirin-Free Regimen for Treating Genotype-1 Hepatitis C Virus Infection Shows Promising Results in a Phase-2b Trial

Results of a phase-2b trial reveal preliminary information about the efficacy of the combination treatment of faldaprevir and deleobuvir for hepatitis C virus infection.

Faldaprevir (a protease inhibitor) and deleobuvir (a nonnucleoside polymerase inhibitor) are 2 components of a combination oral treatment under investigation for treatment of genotype-1 hepatitis C virus (HCV) infection. Scientists from several countries, including Germany, Australia, the United States, Canada, New Zealand, and Germany, collaborated on a phase-2b trial of the combination in development by Boehringer Ingelheim Pharmaceuticals. This trial is known by the acronym SOUND-C2.

Unlike many other trials in HCV treatment, this trial did not exclude patients with cirrhosis. Patients were between 18 and 75 years of age and had HCV RNA levels ≥10,000 IU/mL.

Investigators randomized 362 patients with genotype-1 HCV infection to 1 of 5 treatment options: ribavirin with faldaprevir/deleobuvir 120 mg/600 mg 3 times daily for 16, 28, or 40 weeks; ribavirin with faldaprevir/deleobuvir 120 mg/600 mg twice daily for 28 weeks; or a ribavirin-free regimen with faldaprevir 120 mg daily and deleobuvir 600 mg 3 times daily for 28 weeks.

Patients receiving 28 weeks of the ribavirin-containing regimen were significantly more likely to achieve sustained virologic response than patients receiving 28 weeks of the ribavirin-free regimen (59% sustained virologic response rate versus a 39% rate of sustained virologic response; P = .03).

Common adverse events in this trial included rash, photosensitivity, nausea, vomiting, and diarrhea. In each of the 5 treatment groups, between 89% and 96% of patients experienced at least 1 adverse event. Most adverse events were mild or moderate in severity, which was reflected in the relatively low discontinuation rates due to adverse events, averaging 5% to 11% by group. Severe adverse events included anemia, dehydration, vomiting, rash, photosensitivity, and asthenia, but only vomiting and rash (1 case each) occurred in patients taking the ribavirin-free regimen. Furthermore, none of the 46 patients receiving the ribavirin-free regimen had a hemoglobin level lower than 10 g/dL at any point during the study, compared with 10% to 31% of patients receiving ribavirin-containing regimens, depending on the regimen.

Potential concerns about the all-oral ribavirin-free regimen include its lower likelihood of inducing a 12-week sustained virologic response in patients with genotype-1a HCV. In these patients, only 2 of 18 patients (11%) were functionally cured. More encouraging are results with genotype-1b HCV, in which 16 of 28 patients (57%) experienced a functional cure.

Although ribavirin-free regimens containing faldaprevir and deleobuvir show lower average response rates than ribavirin-containing combinations, this trial provides preliminary evidence that an all-oral ribavirin-free regimen may carry a lower risk of severe hematologic adverse events, such as anemia, compared with a ribavirin-containing regimen.