Bristol-Myers Squibb: PEG-Interferon Lambda
 
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)

The most common AEs reported in at least 10% of patients through Week 12 were:

Adverse Event

PEG-IFN-alfa-2a
(n=10)

All doses of PEG-IFN-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: Investors: John Elicker, 609-252-4611, john.elicker@bms.com
Media: Carrie Fernandez, 609-252-4831, carrie.fernandez@bms.com
Supporting information: The abstract can be viewed on the AASLD website.
 
 
 
 


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