Final results of ACHIEVE-2/3: Albinterferon alfa-2b plus ribavirin in treatment-naive patients with genotype 2/3 chronic hepatitis C.

Background/Aims: ACHIEVE-2/3 - a phase 3, randomized, active-controlled, multicenter study - evaluated the efficacy and safety of albinterferon alfa-2b (albIFN), a genetic fusion polypeptide of albumin and interferon alfa-2b, in patients with genotype 2/3 chronic hepatitis C (CHC). Method(s): In all, 932 patients were randomized 1:1:1 to one of three treatment groups: peginterferon alfa-2a (PEG-IFNalpha-2a) 180 mug qwk, and albIFN 900 and 1,200 mug q2wk for 24 weeks, combined with oral ribavirin 800 mg/d. Randomization was stratified by baseline HCV-RNA >= versus <800,000 IU/mL and genotype 2 versus 3. Primary endpoint: sustained virologic response (SVR; HCV-RNA <15 IU/mL at wk 48). The sample size provided 90% power to demonstrate noninferiority (margin of 12%). Result(s): ACHIEVE-2/3 demonstrated the SVR noninferiority of albIFN 900 mug (P = 0.009) and 1,200 mug (P = 0.006) q2wk versus PEG-IFNalpha-2a 180 mug qwk. By intention-to-treat analysis, SVR rates were 84.8, 79.82, and 80.0% with PEG-IFNalpha-2a, and albIFN 900 and 1,200 mug, respectively. Consistent with previous studies, multivariate analysis identified HCV-RNA <400,000 IU/mL, age <45, BMI <30, genotype 2, normal gamma-glutamyl transferase, high alanine aminotransaminase, no steatosis, fibrosis score 0-2, and Asian region (for PEG-IFNalpha-2a only) as SVR predictors. In the Asian region (n = 271), SVR rates were 95.5, 79.8, and 81.8% with PEG-IFNalpha-2a, and albIFN 900 and 1,200 mug, respectively, versus 80.5, 79.8, and 79.3% in all other regions (n = 662). The incidence of serious (7-8%) or severe (13-16%) AEs, or death (0.3-0.6%) was similar across groups. Discontinuation rates due to AEs were 3.6, 4.8, and 5.5% with PEG-IFNalpha-2a, and albIFN 900 and 1,200 mug, respectively. Severe/serious pulmonary infections and interstitial lung disease were rare, with similar rates across groups. Conclusion(s): ACHIEVE-2/3 demonstrated that albIFN 900 mug q2wk was comparable in efficacy to PEG-IFNalpha-2a 180 mu