Albinterferon alfa‐2b dosed every two or four weeks in interferon‐naïve patients with genotype 1 chronic hepatitis C†‡

Abstract

The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN␣)-2a 180 g one time per week (qwk), or alb-IFN 900 or 1,200 g once every two weeks (q2wk), or 1,200 g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intentionto-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 g q2wk, 55.5% (61/110) with 1,200 g q2wk, and 50.9% (59/116) with 1,200 g q4wk, and 57.9% (66/114) with PEG-IFN␣-2a (P ‫؍‬ 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 g q2wk, 18.2% with 1,200 g q2wk and 12.1% with 1,200 g q4wk, and 6.1% with PEG-IFN␣-2a (P ‫؍‬ 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatmentassociated missed workdays were significantly lower with alb-IFN 900 g q2wk versus PEG-IFN␣-2a (1.1 versus 4.3 days; P ‫؍‬ 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN␣-2a. (HEPATOLOGY 2008;48:407-417.) Abbreviations: AE, adverse event; ANC, absolute neutrophil count; CHC, chronic hepatitis C; CI, confidence interval; EVR12, early virologic response at week 12; HCV, hepatitis C virus; HRQOL, IFN␣, interferon alfa; LOD, limit of detection; LOQ, limit of quantitation; peginterferon alfa; qwk, one time per week; q2wk, once every two weeks; q4wk, once every four weeks; RBV, ribavirin; RVR4, rapid virologic response at week 4; SVR, sustained virologic response; ULN, upper limit of normal. From the 1 J.W. Frankfurt, Germany; 2 University of British Columbia, Vancouver, Canada; Paris, France; 4 Monash University Medical School, Victoria, Australia;5 University of Alberta, Edmonton, Canada; 6 Hadassah University, Jerusalem, Israel;7 Medical University of Bialystok, Poland; Romania; Prague, Czech Republic;10 University of Manitoba, Winnipeg, Canada; 11 Human Genome Sciences Inc., Rockville, MD;and 12 Division of Gastroenterology, Duke Clinical Research Institute, Durham, NC. Received February 21, 2008; accepted April 25, 2008. Supported by Human Genome Sciences Inc., Rockville, MD, and Novartis Pharma AG, Basel, Switzerland (S.Z., E.M.Y., Y.B., S.P., V.G.B., D.S., R.F., V.R., M.G., K.K., J.G.M. Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail: zeuzem@em.uni-frankfurt.de; fax: 49-(0)69-6301-6448. Copyright © 2008 [3][4][5][6][7][8] Approximately 70% ...

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

“…In vivo studies in cynomolgus monkeys revealed a prolonged halflife of alb-IFN in comparison with IFN-a (Osborn et al, 2002). The efficacy of alb-IFN was evaluated in clinical phase IIb studies with IFN-naive patients chronically infected with HCV, in which it was administered every 2 or 4 weeks (Zeuzem et al, 2008). The clinical studies showed that alb-IFN had similar anti-viral effects to pegIFN-a (Nelson et al, 2010;Zeuzem et al, 2010).…”

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…5.3.6 New therapies for hepatitis C Several new therapeutic avenues are being explored for the treatment of hepatitis C. These include new forms of interferon, ribavirin analogues, and direct antiviral agents including protease inhibitors and polymerase inhibitors [222][223][224][225][226][227]. None of these new agents has been subject to clinical trial yet in HIV-positive patients.…”

Viral Hepatitis B und C

“…55,5% und für die 4-wöchige Applikation 50,9%. Im Kontrollarm (Peginterferon alfa-2a) zeigten 57,9% der Patienten eine anhaltende virologische Therapieantwort [26]. In der in Kürze abgeschlossenen Zulassungsstudie wurde auf den 4-wö-chigen Albumin-Interferon-Arm verzichtet.…”