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High Dose Albuferon -early data
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"Week 12 and beyond antiviral activity of higher doses of Albuferon combined with ribavirin in non-responders to prior interferon based therapy for chronic hepatitis C infection"
D. Nelson2; V. Rustgi3; V. Balan4; M. Sulkowski7; L. Lambiase8; R. Dickson5; R. Weisner6; G. Davis9; A. Muir10; L. Novello1; R. Yu1; W. Freimuth1; A. Neumann11; J. McHutchison10; M. Subramanian1
1. Human Genome Sciences, Inc., Rockville, MD, USA.
2. Univ of Florida, Gainesville, FL, USA.
3. Georgetown Univ, Fairfax, VA, USA.
4. Mayo Clinic, Scottsdale, AZ, USA.
5. Mayo Clinic, Rochester, MN, USA.
6. Mayo Clinic, Jacksonville, FL, USA.
7. Johns Hopkins Univ, Baltimore, MD, USA.
8. Univ of Florida, Jacksonville, FL, USA.
9. Baylor Univ Med Ctr, Dallas, TX, USA.
10. Duke University, Raleigh, NC, USA.
11. Bar Ilan Univ, Ramat Gan, Israel.
Background and Aims: Albuferon (alb-IFN) is a novel recombinant protein consisting of IFNa genetically fused to human albumin. This ongoing Phase 2, dose-ranging study evaluates the safety and efficacy of alb-IFN in chronic HCV patients who were non-responders (failed to achieve EVR12 or clear HCV RNA on therapy) to previous IFNa based regimens.
Methods: Subjects were randomized into 3 alb-IFN SC treatment cohorts (900 mcg Q2w, 1200 mcg Q2w or 1200 mcg Q4w) in combination with ribavirin (RBV) 1000-1200 mg/d. After evaluating safety data, 2 higher dose cohorts of alb-IFN 1500 mcg Q2w and 1800 mcg Q2w were enrolled. The treatment duration is 48w with 24w follow-up. The primary efficacy end-point is SVR. The initial 3 cohorts have completed 48w treatment and 12w data for the highest dose cohort is currently available.
Results: Subject demographics and antiviral response for the 115 subjects enrolled are summarized in the table. At w12, the overall antiviral response in the 1800 mcg Q2w cohort was the highest despite having a greater proportion of prior PEG-IFN+RBV non-responders. The slope of HCV RNA decline at w4-12 was significantly more rapid (P<0.01) for the 1800 mcg cohort compared to the 900-1500 mcg cohorts in genotype 1, prior PEG-IFN+RBV non-responders. The w24 antiviral response was comparable across the 900-1500 mcg cohorts. Most patients who were RNA negative at w24 remained negative at w48. Antiviral response at w12 and w24 was predictive of w48 end-of-treatment response for the 900-1200 mcg cohorts. Overall, alb-IFN in combination with RBV was well tolerated and the safety profile in the 1500 mcg and 1800 mcg cohorts was comparable to the 900-1200 mcg cohorts in type, incidence and severity of AEs.
Conclusions: Alb-IFN at doses up to 1800 mcg Q2w in combination with RBV is safe and demonstrates significant antiviral activity in prior IFNa non-responder patients. Further studies are warranted and are ongoing.
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