Pipeline Asset Update for PEG-Interferon Lambda
Pipeline Asset: PEG-Interferon lambda, a novel and potential first-in-class interferon in development for the treatment of hepatitis C virus (HCV) infection
Current Phase of Development: Phase II
Meeting or Publication: American Association for the Study of Liver Diseases (AASLD) 2010
Study Title: Pegylated Interferon Lambda (PEG-IFN-Lambda) Phase II Dose-Ranging, Active-Controlled Study in Combination with Ribavirin (RBV) for Treatment-Naïve HCV Patients (Genotypes 1, 2, 3, or 4): Safety, Viral Response, and Impact of IL-28B Host Genotype through Week 12
Abstract Number: 821
Date/Time of Presentation: Sunday, October 31, 2010 from 8:00 a.m. – 5:30 p.m. EDT
Media Embargo: Per AASLD press guidelines, these data are no longer under embargo.
Study Objective: To assess the safety and antiviral activity of four fixed doses of PEG-IFN-lambda in treatment-naïve patients with HCV genotypes 1, 2, 3, and 4
Study Conclusion: At PEG-IFN-lambda’s three highest dosing levels (120 mcg, 180 mcg, 240 mcg), virologic response at 4 and 12 weeks was similar to or greater than that observed and reported with standard interferons (PEG-IFN-alpha).
Adverse events were mild to moderate in severity and led to few treatment discontinuations.
Efficacy Results: The proportion of patients in each dosing arm that achieved undetectable viral load varied by patient genotype. In this study, undetectable viral load was defined as HCV RNA <25 IU/mL.
Proportion of patients with HCV genotypes 2 or 3 who achieved undetectable viral load:
Dose Week 4 Week 12
PEG-IFN-lambda 80 μg 60% 80%
PEG-IFN-lambda 120 μg 100% 100%
PEG-IFN-lambda 180 μg 80% 80%
PEG-IFN-lambda 240 μg 100% 100%
PEG-IFN-alfa-2a 180 μg 100% 100%
Proportion of patients with HCV genotypes 1 or 4 who achieved undetectable viral load:
Dose Week 4 Week 12
PEG-IFN-lambda 80 μg 14% 14%
PEG-IFN-lambda 120 μg 43% 71%
PEG-IFN-lambda 180 μg 67% 67%
PEG-IFN-lambda 240 μg 43% 43%
PEG-IFN-alfa-2a 180 μg 40% 40%
Adverse Events: The rate of treatment-related serious adverse events (SAEs) through Week 12 was:
-- All doses of PEG-IFN-lambda: 4% (2/45)
-- PEG-IFN-alfa-2a: 10% (1/10)
The rate of discontinuations due to treatment-related adverse events (AEs) through Week 12 was:
-- All doses of PEG-IFN-lambda: 4% (2/45)
-- PEG-IFN-alfa-2a: 10% (1/10)
Adverse Event PEG-IFN-alfa-2a All doses of PEG-IFN-
(n=10) lambda
(n=45)
Myalgia 4 (40%) 6 (13.3%)
Fatigue 3 (30%) 10 (22.2%)
Headache 3 (30%) 10 (22.2%)
Nausea 3 (30%) 10 (22.2%)
Injection site reaction 3 (30%) 9 (20%)
Depression 2 (20%) 6 (13.3%)
Pruritus 1 (10%) 5 (11.1%)
Vomiting 1 (10%) 5 (11.1%)
Irritability 1 (10%) 11 (24.4%)
Insomnia 0 11 (24.4%)
The majority of PEG-IFN-lambda adverse events were mild to moderate in severity. No apparent dose relationship was observed.
PEG-IFN-lambda Background: PEG-IFN-lambda is a novel and potential first-in-class interferon in development for the treatment of hepatitis C. The native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than type I interferons such as interferon alpha. Because this receptor is present on fewer cell types within the human body, it is hypothesized that PEG-Interferon lambda may be able to demonstrate an improved safety and tolerability profile compared to alpha interferons.
PEG-IFN-lambda is one of several molecules Bristol-Myers Squibb is studying for the potential treatment of hepatitis C. The portfolio of investigational compounds, which also includes several small molecule direct-acting antivirals, fits into the company’s overall R&D focus on diseases where there is major unmet medical need.
Study Background: The EMERGE study is a two-part, randomized, controlled, multicenter phase II, phase II study of PEG-IFN lambda in treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4.
These data are from the first part of the EMERGE study. In this ongoing, open-label Phase IIa study, 55 patients were randomized to receive PEG-IFN-lambda at one of four dose levels (80, 120, 180 or 240 mg) or PEG-IFN-alpha at 180 μg. Patients received PEG-IFN lambda and PEG-IFN alpha administered subcutaneously on a weekly basis, as well as ribavirin on a daily basis, dosed according to HCV genotype and body weight. Patients with HCV genotype 2 or 3 were studied for up to 24 weeks; patients with genotype 1 or 4 were studied for up to 48 weeks.
Inclusion Criteria:
-- 18 to 70 years of age
-- HCV genotype 1, 2, 3, or 4 with HCV RNA ≥100,000 IU/mL at screening
-- Naïve to prior IFN therapy
-- ALT, AST ≤5.0x ULN; INR ≤1.2; bilirubin ≤1.5 mg/dL; albumin ≤ULN
-- No evidence of decompensated liver disease or cirrhosis
Exclusion Criteria:
-- Mixed genotype HCV infection
-- History of decompensated liver disease
-- Co-infection with HIV or hepatitis B virus
-- Active substance abuse
ClinicalTrials.gov Identifier: NCT01001754
Request for More Information and Media Interviews: Invest
ors: John Elicker, 609-252-4611, john.elicker@bms.com
Media: Cristi Barnett, 609-252-6028, cristi.barnett@bms.com
Supporting information: The abstract can be viewed on the AASLD website.
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