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J Hepatol. 2014 Dec;61(6):1238-46. doi: 10.1016/j.jhep.2014.07.022. Epub 2014 Jul 24.

A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection.

Author information

1
Duke Clinical Research Institute, Duke University, Durham, NC, USA.
2
University of New Mexico, Albuquerque, NM, USA.
3
University of Colorado Denver & Hospital, Aurora, CO, USA.
4
Medical University of Białystok, Białystok, Poland.
5
Westmead Hospital, Westmead Millennium Institute and University of Sydney, Westmead, NSW, Australia.
6
Texas Clinical Research Institute, Arlington, TX, USA.
7
Henry Ford Hospital, Detroit, MI, USA.
8
ZymoGenetics, Bristol-Myers Squibb, Seattle, WA, USA.
9
Toronto Digestive Disease Associates, Inc., Vaughan, ON, Canada.
10
SCTI Research Foundation, Coronado, CA, USA.
11
Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
12
Weill Cornell Medical College, New York, NY, USA.
13
Miami VA Medical Center, Miami, FL, USA.
14
Virginia Mason Medical Center, Seattle, WA, USA.
15
The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
16
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
17
Fundación de Investigación, San Juan, Puerto Rico.
18
Metropolitan Research, Fairfax, VA, USA.
19
Liver Institute of Virginia, Newport News/Richmond, VA, USA.
20
Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA. Electronic address: subasree.srinivasan@bms.com.
21
Mayo Clinic in Arizona, Phoenix, AZ, USA.
22
Advanced Liver Therapies at St. Luke's Episcopal Hospital, Baylor College of Medicine, Houston, TX, USA.
23
Department of Medicine, JW Goethe University Hospital, Frankfurt, Germany.

Abstract

BACKGROUND & AIMS:

Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events.

METHODS:

This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks.

RESULTS:

Rates of undetectable HCV-RNA at week 12 (complete early virologic response [cEVR]; primary end point) were significantly higher in GT1,4 patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA at week 4 were significantly higher on 180 μg (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 μg (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103, 6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week 24) were comparable between Lambda and alfa for GT1,4 (37-46% Lambda; 37% alfa) and GT2,3 (60-76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240 to 180 μg dose reduction was therefore implemented. Serious adverse events were comparable (3-13% Lambda; 3-7% alfa). Grade 3-4 haemoglobin, neutrophil, and platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133 (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda demonstrated fewer musculoskeletal (16-28% vs. 47-63%) and influenza-like events (8-23% vs. 40-46%) than alfa.

CONCLUSION:

Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection.

KEYWORDS:

Efficacy; SVR; Safety; Treatment-naive; Type III interferon

PMID:
25064437
DOI:
10.1016/j.jhep.2014.07.022
[Indexed for MEDLINE]

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