LONDON — Sustained virologic response rates at 12 weeks were more than 90% across several treatment groups in a cohort of patients who previously failed pegylated interferon and ribavirin therapy who received ritonavir-boosted ABT-450, ABT-267 and ABT-333 with ribavirin.
Stefan Zeuzem, MD, of J.W. Goethe University in Frankfurt, Germany, presented results of the SAPPHIRE II study at The International Liver Congress 2014. Zeuzem noted that the success of retreatment of HCV patients who have failed prior therapy may be dependent on treatment history. Null responders to pegylated interferon and ribavirin therapy have demonstrated the lowest responses.
The current study investigated a regimen that included the NS3/4A protease inhibitor ABT-450 dosed with 100 mg ritonavir (Enanta), known as ABT-450/r, plus the NS5A inhibitor ABT-267 and the NS5B RNA polymerase inhibitor ABT-333 (all AbbVie).
Eligible participants in the double blind, placebo-controlled trial were non-cirrhotic patients with HCV genotype 1 infection. “Baseline characteristics were well balanced across the cohort,” Zeuzem said. “The key characteristics were that the average age was [approximately] 55 years and patients had mild to moderate fibrosis.”
Patients were randomly assigned 3:1 to the three-drug regimen plus weight-based ribavirin or matching placebo for 12 weeks. “The SVR rate was calculated from a predefined historical rate associated with telaprevir plus pegylated interferon and ribavirin,” Zeuzem said.
The final analysis included 297 patients in the active-therapy group and 97 patients in the placebo group.
The 12-week sustained viral response (SVR12) rate was 96.3% for the active-therapy group. Virologic failure was reported in 2.4% of the cohort. “These rates were clearly passing the predefined noninferiority threshold and the superiority threshold,” Zeuzem said.
The SVR12 rate was 95.3% for prior pegylated interferon/ribavirin relapsers, 100% for partial-responders and 95.2% for null responders.
“SVR rates were high across all prior pegylated interferon/ribavirin response groups,” Zeuzem said.
SVR rates were high regardless of HCV genotype, according to Zeuzem.
An SVR12 rate of 96% was reported in patients with genotype 1a infection and a rate of 96.7% in patients with genotype 1b infectious.
“Not a single patient showed a virologic breakthrough,” he added.
The most common adverse events in the overall cohort were headache (36.4% in active-therapy group, 35.1% in placebo group) and (33.3% and 22.7%, respectively). However, there was no significant difference between the two groups in the rate of these adverse events (P>.05). In addition, the rate of anemia was less than 5%, Zeuzem said.
“The rate of patients who discontinued prematurely was very low,” he said, adding that rates of discontinuation related to adverse events were 1% in the active-therapy group and 0% in the placebo group.
“Three patients discontinued the study drug due to adverse events,” he said. – by Rob Volansky
For more information:
Zeuzem S. Abstract #01. Presented at: The International Liver Congress 2014; April 9-13, 2014; London.
Disclosure: Zeuzem reports consultancies for Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Idenix, Janssen, Merck, Novartis, Roche, Santaris and Vertex.