| 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: Cristi Barnett, 609-252-6028, cristi.barnett@bms.com |
| Supporting information: |
The abstract can be viewed on the AASLD website. |