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Interferon-free triple regimen plus ribavirin effective in previously untreated patients
LONDON — A 12-week multitargeted regimen of AbbVie’s ABT-450 with ritonavir, ombitasvir and dasabuvir in combination with ribavirin was highly effective and associated with a low rate of treatment discontinuation among previously untreated patients with hepatitis C virus genotype 1 infection and no cirrhosis, according to new data from the SAPPHIRE I study.
Jordan J. Feld, MD, MPH, from Toronto Western Hospital Liver Centre in Toronto and a member of the HCV Next Editorial Board, presented data on the safety and efficacy of the NS3/4A protease inhibitor ABT-450 with ritonavir, the NS5A inhibitor ombitasvir (formerly ABT-267) and the NS5B RNA polymerase inhibitor dasabuvir (formerly ABT-333) in combination with ribavirin. As this interferon-free regimen has previously demonstrated efficacy in patients with HCV genotype 1 infection, the researchers wanted to evaluate this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
Patients were randomly assigned in a 3:1 ratio to a single-tablet coformulation of ABT-450/r-ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice daily) with weight-based ribavirin or to matching placebo. The active-therapy group included 472 patients and the placebo group included 158 patients. Each group was treated for 12 weeks.
“Patients in the placebo group were rolled over into active treatment for an additional 12 weeks,” Feld said at the meeting. “We followed patients for 48 weeks from active dosing.”
Sustained virologic response at 12 weeks (SVR12) in an intention-to-treat analysis served as the primary endpoint. Noninferiority and superiority outcomes were measured in comparison with previous results for telaprevir (Incivek, Vertex), pegylated interferon and ribavirin. Secondary endpoints included SVR12 by subtype, breakthrough and relapse rates. Safety in terms of adverse events and laboratory abnormalities also were evaluated.
“The cohort was mostly white, with 40% of patients from America, 40% from Europe and 20% from elsewhere,” Feld said. The median patient age was 52 years.
The SVR12 rate in the intent-to-treat analysis for patients in the active-therapy group was 96.2% (95% CI, 94.5-97.9). “This was above both noninferiority and superiority thresholds,” Feld said.
Additional results indicated that the rate of response rates in the active-therapy group were 95.3% for patients with HCV genotype 1a and 98% for patients with genotype 1b.
“SVR12 rates across all patient subgroups were above 90%,” Feld said. “There was no difference with regard to male or female [gender], race, BMI, fibrosis stage, or whether ribavirin dose modification was required.”
Eight virologic failures were reported, including one breakthrough and seven relapses, according to Feld. This amounted to a breakthrough rate of 0.2% and a relapse rate of 1.5% in the active-therapy group.
Feld noted that “a fairly high proportion” of patients in the active-therapy group experienced adverse events. The overall rate of adverse events during the double blind study period was 87.5% in the active-therapy group vs. 73.4% in the placebo group (P<.001). Most adverse events were mild. The rate of serious adverse events was 2.1% in the active-therapy group. “Only two of those patients had events that were related to treatment [with the coformulated three-drug regimen],” Feld said.
The rate of discontinuation related to adverse events was 0.6% in both groups. Fatigue and headache were reported at a similar rate in the active-therapy and placebo groups, but nausea, pruritus, insomnia, diarrhea and asthenia occurred in significantly more patients in the active-therapy group (P<.05 for all comparisons).
Regarding laboratory abnormalities, ALT and AST were less than 1% in the active therapy group, according to Feld. He added that bilirubin elevations were seen in 2.8% of the active therapy cohort, but most of those events were transient. – by Rob Volansky
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Disclosure: Feld reports associations with AbbVie and Boehringer Ingelheim.