Biotech Values

[dewophile]

ZGEN
AASLD abstract
(note that the drug was tested in a weekly and biweekly regimen. data below represent the lowest dose cohort given drug on days 1 and 15)

Interim Results from a Phase 1b Dose-Escalation Study of 4 Weeks of PEG-Interferon Lambda (PEG-rIL-29) Treatment in Subjects with Hepatitis C Virus (HCV) Genotype 1 with Prior Virologic Response and Relapse to Peginterferon Alfa and Ribavirin
E. J. Lawitz1; A. Zaman2; A. J. Muir3; M. L. Shiffman4; B. Yoffe5; T. Zhang6; S. Souza6; D. F. Hausman6
1. Alamo Medical Research, San Antonio, TX, USA.
2. Oregon Health & Science University, Portland, OR, USA.
3. Duke University, Durham, NC, USA.
4. Virginia Commonwealth University Medical Center, Richmond, VA, USA.
5. Baylor College of Medicine/MEDVAMC, Houston, TX, USA.
6. ZymoGenetics Inc, Seattle, WA, USA.



PEG-interferon lambda is a novel Type III interferon (IFN) that binds to a unique receptor complex with a more limited distribution than the receptor for Type I IFNs. In a Phase 1 dose-escalation study in healthy volunteers, PEG-IFN lambda was pharmacologically active and well-tolerated without flu-like symptoms or hematologic effects. A Phase 1b study was initiated to evaluate the safety and efficacy of PEG-IFN lambda in subjects with genotype 1 HCV who had previously relapsed following peginterferon alfa and ribavirin therapy.

Methods: This open-label, dose- and schedule-escalation study is evaluating PEG-IFN lambda administered subcutaneously either every other week (QoW) on Days 1 and 15 or weekly over a 4-week period in cohorts of 6 subjects each. HCV RNA was assessed prior to dosing on Days 1, 2, 4, 8, 15, 22 and 29.

Results: Cohort 1 (1.5 μg/kg PEG-IFN lambda QoW) has been completed; enrollment into Cohort 2 (3.0 μg/kg QoW) is ongoing. 6 subjects (4 M, 2 F) were treated in Cohort 1, mean age = 53 yrs, mean baseline log10 HCV RNA = 7.3. Treatment was well-tolerated with no dose reductions or discontinuations. No subject experienced fever related to PEG-IFN lambda dosing. Adverse events, all Grade 1-2, were reported for 1 of 6 subjects and included myalgia, fatigue and irritability considered possibly related to PEG-IFN lambda in the setting of a concurrent, unrelated respiratory infection. All laboratory abnormalities were Grade 1 or 2. No subject had a clinically significant increase from baseline in ALT, AST or bilirubin during treatment and 1 of 4 subjects with baseline elevation had normalization of ALT. No hematologic toxicities were seen. Antiviral activity, defined as a decrease of ≥1-log10 in HCV RNA, was observed in 4/6 subjects. The mean maximum log decrease any time on study was 2.15 (range 0.59-5.18;Table 1).

Conclusions: Repeat dosing with PEG-IFN lambda was well-tolerated and associated with antiviral activity. Five of six subjects reported no adverse events. Data on additional cohorts will be presented at the meeting. Continued evaluation of the safety and antiviral activity of PEG-IFN lambda, both alone and in combination with ribavirin, is planned.



Table 1. Log10 Decrease in HCV RNA Subj 1 Subj 2 Subj 3 Subj 4 Subj 5 Subj 6
Baseline
(Day 1) 7.56 7.37 7.29 7.08 7.52 7.24
Day 4 -2.46 -0.59 -3.71 -1.90 -1.95 -0.72
Day 8 -1.74 -0.21 -2.73 -0.63 -0.95 -0.66
Day 15 -0.69 -0.37 -3.71 -0.86 -0.26 -0.25
Day 22 -1.70 -0.24 -5.18 -1.29 -1.24 -0.76
Day 29 -0.65 -0.37 -4.80 -0.67 -0.35 -0.3
PEG-IFN lambda administered on Days 1 and 15.