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Albuferon + Ribavirin in PegIFN Nonresponders: phase 2 study
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Reported by Jules Levin
http://www.natap.org
from AASLD
Nov 14, 2005, San Francisco
D Nelson, University of Florida, Gainesville, FL; Human Genome Sciences, Inc.,
Rockville, MD
Today at the final oral session & the last talk was presented by Don Nelson, not the former basketball player, and presented very interesting data on Albuferon. After his talk he commented that they did not see injection site reactions as a problem, and a large phase II study of 450 patients was ongoing. At EASL in the Spring study data showed 3-4 log reductions in viral load at day 28 with 900-1200 dosing.
Albuferon is a novel recombinant protein consisting of IFNa genetically fused to human serum albumin. The resulting molecule combines the antiviral properties of IFN with the prolonged serum half-life of albumin.
This Phase 2, randomized, dose-ranging study is being conducted in chronic HCV patients (CHC) who were non-responders (NR) to previous treatment with IFNa containing regimens. Albuferon is administered by subcutaneous injection. Two-thirds of the patients in this study were pegIFN nonresponders & received at least 1 prior therapy.
71 subjects were enrolled in parallel into 3 Albuferon SC treatment cohorts (900 ug Q2w (once every 2 weeks injection), 1200 ug Q2w or 1200 ug Q4w (once every 4 weeks) in combination with ribavirin (RBV) 1000-1200 mg/d. The treatment duration is 48w with 24w follow-up and the primary efficacy end-point is SVR. Following evaluation of 8w of safety data, 22 subjects were enrolled in a 4th treatment cohort of Albuferon 1500 ug Q2w with RBV. Dose escalation to 1500 & 1800 is occurring.
Interim results:
The majority of subjects enrolled were non-responders to PEG-IFNa RBV therapy (70%) and were infected with genotype 1 HCV (93%). Subject demographics and antiviral response is summarized in the table.
Safety (up to w12): Albuferon in combination with RBV was well tolerated. No subject required dose reduction for the management of non-hematologic adverse events. The most common adverse events were fatigue (73%), headache (63%), myalgia (52%) and nausea (42%). No subject required discontinuation of Albuferon or ribavirin for hematologic abnormalities. Erythropoetin (EPO)
was allowed for Hb
PK: Albuferon has a t1/2 of 6 days. Over the first 12w of therapy, accumulation in Albuferon serum concentrations was observed in the Q2w cohorts (60-80%) with minimal accumulation in the Q4w cohort.
Antiviral response (up to w24): The antiviral response at w12 and w24 was comparable in the Q2w and Q4w groups. EVR12 was observed in 45% and 31% of subjects were HCV RNA negative at w24.
Albuferon in combination with ribavirin appears safe, well tolerated and shows antiviral activity in IFNa non-responders. The data supports further evaluation of the Albuferon dosing schedule of Q2w and Q4w administration in subjects with CHC.
At week 12, the Early Viral response (>/= 2 logs) was 52% in the 900 Q2w group, 42% in the 1200 Q2w group, and 42% in the 1200 Q2w group. At week 12 21% in the 900 group, 17% in the 1200 Q2 group, and 30% in the 1200 Q4 group had undetectable HCV RNA. At week 24, 35% in the Q2W group was HCV RNA negative, 29% (not 33% as it says in pic below) were HCV RNA negative in the 1200 Q2W group, and 25% in the Q4W group were HCV RNA negative.
At week 24 viral load reduction was -3.5 log in the 900 group & -2.5 log in the pooled 1200 mg groups.
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