Locteron Viral Kinetics and Anti-Viral Activity during Treatment with a Controll

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Locteron Viral Kinetics and Anti-Viral Activity during Treatment with

a Controlled-Release Interferon Alfa-2b in Genotype 1 Chronic

Hepatitis C Patients

--see attached report containing graphs and tables

Reported by Jules Levin

43rd EASL

April 23-27, 2008

Milan, Italy

E. Herrmann1, S. Zeuzem2, I. Dziublyk3, L. Moroz4, I. Zaytsev5, S.

Martens2, E. van Hoogdalem6, J. Humphries7

1Saarland University, Homburg/Saar, Germany; 2J.W. Goethe-University

Hospital furt; 3National Medical Academy, Kiev, Ukraine;

4National Medical University, Vinnitsa, Ukraine; 5State Medical

University, Donetsk, Ukraine; 6OctoPlus N.V., Leiden, The Netherlands;

7Biolex Therapeutics, Pittsboro, NC, USA

AUTHOR CONCLUSIONS

In this study, Locteron, a controlled-release formulation of

unmodified IFN-alfa2b, administered every 2 weeks to treatment-naïve

patients with chronic hepatitis C (genotype 1) demonstrated strong

anti-viral activity combined with an improved safety and tolerability

profile compared to currently marketed interferons and those in

development.

Viral kinetic analysis demonstrated a dose-dependent anti-viral

efficiency with a decrease of ALT levels. Furthermore, OAS levels and

neopterin concentrations increased dose-dependently early during

treatment.

BACKGROUND

Controlled-release recombinant interferon alfa2b (IFN-alfa2b,

Locteron) is a novel approach to delivery of interferon. As a result

of the slow release of high doses of interferon (up to 200 MIU),

tolerability is importantly improved over pegylated interferons, with

similar if not improved efficacy, in addition to less frequent dosing.

STUDY OBJECTIVE

A Phase 2a, open-label, dose-ranging study was conducted in treatment-

naïve patients with genotype 1 chronic HCV infection to evaluate the

safety and anti-viral effect of Locteron. Here, we analyzed viral

kinetics as well as kinetics of alanine aminotransferase (ALT), 2'3'-

oligoadenylate synthetase (OAS) and neopterin concentrations.

METHODS

Thirty-two patients were randomized to receive subcutaneous

injections of Locteron 14 days apart over 12 weeks in 4 dose cohorts

(8 per cohort) of 160, 320, 480 and 640 ug, with the 640 ug group

starting after safety evaluation of the other cohorts. All subjects

received weight-based ribavirin between 800-1400 mg/day. Analysis of

IFN-alfa2b in human serum samples was performed by a modified ELISA

from GE HealthCare, UK, using standards and quality controls prepared

from IFN-alfa2b (BLX-883). LLOQ for IFNalfa2b using the ELISA was 2.5

pg/mL (A. Kromminga, IPM, Hamburg, Germany).

Viral kinetics for the first 4 weeks were modeled mathematically from

a full PK-PD model according to the individual pharmacokinetic

profile of Locteron for all patients. The compartmental model was

based on a differential equation system including a time-varying

efficiency factor according to the respective serum levels of

Locteron.

Furthermore, ALT, OAS and neopterin concentrations were evaluated.