Faldaprevir and deleobuvir for HCV genotype 1 infection.
BACKGROUND
Interferon-free regimens would be a major advance in the treatment of patients with chronic hepatitis C virus (HCV) infection.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.).
Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. zeuzem@em.uni-frankfurt.de
Stefan
S
Zeuzem
Vincent
V
Soriano
Tarik
T
Asselah
Jean-Pierre
JP
Bronowicki
Ansgar W
AW
Lohse
Beat
B
Müllhaupt
Marcus
M
Schuchmann
Marc
M
Bourlière
Maria
M
Buti
Stuart K
SK
Roberts
Ed J
EJ
Gane
Jerry O
JO
Stern
Richard
R
Vinisko
George
G
Kukolj
John-Paul
JP
Gallivan
Wulf-Otto
WO
Böcher
Federico J
FJ
Mensa
D000328:Adult; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011480:Protease Inhibitors; D011804:Quinolines; D013844:Thiazoles; C552340:faldaprevir; D011392:Proline; D012321:DNA-Directed RNA Polymerases; D007930:Leucine