Yu, J, Sun, H, Pang, M, Chuang, W, Sarin, SK, Flisiak, R and Stein, DS (2014) Population pharmacokinetics and pharmacodynamics of albinterferon alfa-2b in patients treated for hepatitis C virus genotype 2/3. Anti-Infective Agents. pp. 58-67.

Abstract

Albinterferon alfa-2b (albIFN) has been studied for the treatment of chronic hepatitis C virus infection in combination with ribavirin at different dose regimens ranging 900-1500 mug once every 2 (q2w) or 4 (q4w) weeks. Analyses on efficacy and safety exposure-response relationships in Genotype2/3 (G2/3) interferon-naive patients were conducted to explore an improved risk-benefit of therapy. Data from 972 G2/3 patients were included in the exposure-response analysis. Major antiviral response endpoints of Sustained Virologic Response (SVR) and Rapid Virologic Response (RVR) exposure- response were modeled using logistic regression. The reported adverse event AE frequencies were tabulated vs quartiles of albIFN exposure. Body weight based exposure were estimated based on the population pharmacokinetic (PK) model and simulations were performed according to the weight based exposure and the exposure-response relationship. Within the G2/3 interferon-naive patients, albIFN Cavg but not Cmax or Cmin was associated with efficacy, along with certain baseline characteristics. For a given Cavg, dosing q2w was more active than q4w for RVR; Cavg was modestly associated with SVR, while no effect of dose interval was observed. Cavg was associated with a number of adverse events and laboratory abnormalities, especially at the higher exposure quartiles. The weight-based dose regimen (20 mug/kg) was predicted to decrease the subjects in the higher two quartiles of exposure by about half, compared with the fixed 1500 mug dose. This potential improvement was predicted to have a better overall safety profile with similar efficacy, but the overall reduction in AE's would be small. As albIFN Cavg was significantly associated with both efficacy and safety outcomes, a weight-based regimen would be unlikely to significantly improve the risk benefit in comparison to the standard of care. 2014 Bentham Science Publishers

Item Type:	Article
Additional Information:	NIBR author: Yu, J institute: NIBR contributor address: (Yu) Modeling and Simulation Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals Inc, Cambridge, MA, United States (Sun) Drug Metabolism and Pharmacokinetics, Novartis Pharmaceuticals, Inc, East Hanover, NJ, United States (Pang) Clinical Operations, Novartis Pharmaceuticals, Inc, East Hanover, NJ, United States (Chuang) Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals, Inc, East Hanover, NJ, United States (Chuang) Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (Republic of China) (Sarin) Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India (Flisiak) Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland (Stein) Translational Medicine, Novartis Pharmaceuticals, Inc, East Hanover, NJ, United States
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22581