October 31, 2010

BMS posts data update on investigational compound PEG-IFN lambda for hepatitis C, Data presented at AASLD today

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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