Some Chronic Hepatitis C Patients Failing Interferon/Ribavirin Achieve Sustained Virological Response with Albinterferon Alfa-2b

Albinterferon (albumin interferon alfa) is a recombinant protein consisting of interferon alfa-2b genetically fused to the human albumin protein. Presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston, MA (November 2-6, 2007), the current randomized Phase 2 study evaluated the efficacy and safety of albinterferon in combination with weight-based ribavirin for HCV patients who were non-responders to prior treatment with pegylated interferon plus ribavirin.

Study participants (n=115) received one of 3 albinterferon regimens (900 mcg every 2 weeks, 1200 mcg every 2 weeks or 1200 mcg every 4 weeks) in combination with oral weight-based ribavirin 1000-1200 mg/day. After evaluating safety data, 2 additional cohorts were treated with higher doses of albinterferon (1500 mcg every 2 weeks and 1800 mcg every 2 weeks), for a total of 5 dosing arms.

Treatment duration was 48 weeks and the primary efficacy endpoint was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after the completion of treatment. The protocol was amended to allow extended treatment (for a total of 72 weeks) for slow responders (i.e., subjects who became HCV RNA negative after week 24).

Results

• The demographics and virological response rates for the 115 enrolled patients are summarized in the table below.

• The 1500 and 1800 mcg dose groups included more patients with baseline characteristics associated with poor response (e.g., high pre-treatment HCV RNA, pegylated interferon/ribavirin non-responder, African-American).

• All albinterferon doses were well tolerated and the safety profile in the 1500 mcg and 1800 mcg cohorts was comparable to that of the 900-1200 mcg cohorts in incidence and types of adverse events.

• The overall SVR rate for the first 4 treatment groups was 19% (18 of 93).

• SVR was lower in the genotype 1 pegylated interferon/ribavirin non-responder group, at 12% (7 of 57).

• Importantly, the 1800 mcg group showed robust antiviral response -- 50% (6 of 12) achieved early virological response at 12 weeks -- in genotype 1 “null responders” to prior pegylated interferon/ribavirin therapy.

• However, higher albinterferon dosing did not produce higher SVR rates.

• The most frequently reported adverse effects were fatigue and headache.

• There was a low incidence of anemia and neutropenia.

• Similar numbers of patients discontinued treatment across all arms.

Based on these results, the investigators concluded, “Albinterferon in combination with oral ribavirin is safe and effective. Treatment with 1800 mcg [every 2 weeks] demonstrates significant antiviral activity in prior interferon alfa non-responder patients.”

University of Florida, Gainesville, FL, USA; Metropolitan Research, Arlington, VA, USA; Mayo Clinic, Scottsdale, AZ, USA; Johns Hopkins University, Baltimore, MD, USA;  Baylor University Medical Center, Dallas, TX, USA; Duke University, Durham, NC, USA; University of Florida, Jacksonville, FL, USA;  Mayo Clinic, Jacksonville, FL, USA; Mayo Clinic, Rochester, MN, USA; Duke Clinical Research Institute, Durham, VA, USA; Human Genome Sciences, Rockville, MD, USA.

11/13/07

Reference
DR Nelson, VK Rustgi, V Balan, M. Sulkowski, and others. Sustained Virologic Response with albinterferon alfa-2b/ribavirin treatment in prior interferon therapy non-responders. 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007). Boston, MA. November 2-6, 2007. Abstract (oral) 51.