ORIGINAL ARTICLE
Faldaprevir and Deleobuvir for HCV Genotype 1 Infection
Stefan Zeuzem, M.D., Vincent Soriano, M.D., Ph.D., Tarik Asselah, M.D., Ph.D., Jean-Pierre Bronowicki, M.D., Ph.D., Ansgar W. Lohse, M.D., Beat Müllhaupt, M.D., Marcus Schuchmann, M.D., Marc Bourlière, M.D., Maria Buti, M.D., Stuart K. Roberts, M.D., Ed J. Gane, M.D., Jerry O. Stern, M.D., Richard Vinisko, M.A., George Kukolj, Ph.D., John-Paul Gallivan, Ph.D., Wulf-Otto Böcher, M.D., and Federico J. Mensa, M.D.
N Engl J Med 2013; 369:630-639 August 15, 2013 DOI: 10.1056/NEJMoa1213557
Interferon-free regimens would be a major advance in the treatment of patients with chronic hepatitis C virus (HCV) infection.
In this phase 2b, randomized, open-label trial of faldaprevir (a protease inhibitor) and deleobuvir (a nonnucleoside polymerase inhibitor), we randomly assigned 362 previously untreated patients with HCV genotype 1 infection to one of five groups: faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily, plus ribavirin, for 16, 28, or 40 weeks (TID16W, TID28W, or TID40W, respectively); faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg twice daily, plus ribavirin, for 28 weeks (BID28W); or faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily, without ribavirin, for 28 weeks (TID28W-NR). The primary end point was a sustained virologic response 12 weeks after the completion of therapy.
The primary end point was met in 59% of patients in the TID16W group, 59% of patients in the TID28W group, 52% of patients in the TID40W group, 69% of patients in the BID28W group, and 39% of patients in the TID28W-NR group. The sustained virologic response 12 weeks after the completion of therapy did not differ significantly according to treatment duration or dosage among ribavirin-containing regimens. This response was significantly higher with TID28W than with TID28W-NR (P=0.03). Rates of a sustained virologic response 12 weeks after the completion of therapy were 56 to 85% among patients with genotype 1b infection versus 11 to 47% among patients with genotype 1a infection and 58 to 84% among patients with IL28B CC versus 33 to 64% with non-CC genotypes. Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events.
The rate of a sustained virologic response 12 weeks after the completion of therapy was 52 to 69% among patients who received interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin. (Funded by Boehringer Ingelheim; SOUND-C2 ClinicalTrials.gov number, NCT01132313.)