Antiviral Activity, Pharmacodynamics, and Quality of Life in Genotype 1 Hepatitis C Patients Treated with Albinterferon (Albuferon)

By Liz Highleyman

Albinterferon alfa-2b (albumin interferon; brand name Albuferon) is created by fusing interferon alfa with the human blood protein albumin, which enables it to last longer in the body. Albinterferon may be administered once every 2 to 4 weeks, compared with 3 times weekly for conventional interferon alfa and once-weekly for pegylated interferon alfa (Pegasys or PegIntron).

A recently published Phase 2 study found that albinterferon administered at 4-week intervals was safe and well-tolerated in patients with genotype 2 or 3 chronic hepatitis C virus (HCV) infection.

Two studies presented at the Digestive Disease Week (DDW) 2008 conference last week in San Diego assessed the use of albinterferon in genotype 1 patients.

Viral Kinetics and Pharmacodynamics

In the first study, Avidan Neumann and colleagues studied the viral kinetics and pharmacodynamics of albinterferon. As background, they noted that prior research has indicated that continued adequate concentrations of interferon are important in reducing the emergence of drug resistance mutations during treatment with specifically-targeted antiviral therapy (dubbed "STAT-C"), such as HCV protease and polymerase inhibitors currently under development.

The present study included 26 interferon-naive participants with genotype 1 chronic hepatitis C. Patients received 900 mcg or 1200 mcg albinterferon alfa-2b every 2 weeks. Over the course of 42 days, the investigators frequently measured drug levels and HCV RNA using a polymerase chain reaction (PCR) assay with a lower limit of detection of 10 IU/mL.

Antiviral response as a function of albinterferon serum levels was determined by 90% effective concentration (EC90) and second-order sensitivity to changes in albinterferon levels.

Results

• A large first phase viral decline of 1.65 log10 IU/mL and a rapid second phase slope of 0.5 log/week were observed.

• The albinterferon EC90 was 4.3 log pg/mL, with an effective quotient (Cmax/ EC90) of 2.6.

• 14 days after injection, albinterferon still exhibited an inhibitory quotient of 1.5.

• Drug levels were in excess of the EC90 for a median of 14 days, thus preventing viral rebound in most patients.

• Second-order sensitivity to changes in albinterferon level was low (Nhill 1.0), which together with the drug's long half-life led to slow viral rebound in the few patients who experienced rebound.

• 12 of 14 patients (86%) with a > 2 log reduction in HCV RNA at week 4 achieved sustained virological response with 48 weeks of albinterferon in a subsequent Phase 2b study.

Based on these findings, the investigators concluded that, "Albinterferon alfa-2b 900 and 1200 mcg exhibited remarkable pharmacodynamic properties, maintaining high antiviral effectiveness for a prolonged duration, and could be effectively used in combination with STAT-C drugs to prevent development of resistance."

Health-related Quality of Life

In the second study, an international team of researchers evaluated the efficacy, safety, and health-related quality of life (HRQOL) of albinterferon plus ribavirin in genotype 1 chronic hepatitis C patients.

In this Phase 2b clinical trial, 458 interferon-naive participants were randomly assigned to receive one of 4 regimens, all in combination with ribavirin:

• Albinterferon 900 mg every 2 weeks;

• Albinterferon 1200 mg every 2 weeks;

• Albinterferon 1200 mg every 4 weeks;

• Pegylated interferon 180 mcg/week (standard therapy).

The primary efficacy endpoint was sustained virologic response (SVR), or continued undetectable HCV RNA 24 weeks after completion of therapy. HRQOL was assessed by changes in SF-36 v2 (a standard self-report quality of life assessment tool). SF-36 was evaluated at baseline, weeks 4, 12, 24, and 48 on treatment, and weeks 4, 12, and 24 post-treatment. Patient disability was evaluated based on number of missed workdays or days with impaired activity.

Results

• In an intention-to-treat analysis, SVR rates were statistically similar across treatment arms:

• 58.5% for albinterferon 900 mcg;
• 55.5% for albinterferon 1200 mcg every 2 weeks;
• 50.9% for albinterferon 1200 mcg every 4 weeks;
• 57.9% for pegylated interferon.

• Overall, albinterferon had less impact on the SF-36 physical and mental domains during treatment compared with pegylated interferon.

• Reductions in SF-36 scores occurred by week 4-12, consistent with the occurrence of most treatment-associated adverse events.

• At week 12, there was significantly less worsening in SF-36 physical (P = 0.04) and mental (P = 0.02) component scores, as well as role-physical (P = 0.02), bodily pain (P = 0.003), vitality (P = 0.02), social-functioning (P < 0.001), and mental health (P = 0.003) scores with 900 mcg albinterferon compared with pegylated interferon.

• Disability day assessments were significantly more favorable with albinterferon 900 mcg than with pegylated interferon.

• The proportion of patients with 7 or more missed workdays in the month prior to assessment was significantly lower with 900 mcg albinterferon than with pegylated interferon at week 12 (4.2% vs 18.1%; P = 0.006) and week 24 (5.3% vs 20.3%; P = 0.005).

• Quality of life and disability results for 1200 mcg albinterferon every 2 or 4 weeks were generally comparable to those for pegylated interferon.

The investigators concluded that the 900 mcg albinterferon every 2 weeks regimen "was associated with significantly more favorable HRQOL and fewer missed workdays, while maintaining efficacy at least comparable to that of [pegylated interferon]."

5/23/08

References

AU Neumann, L Rozenberg, VG Bain, and others. Viral kinetics and pharmacodynamics of albinterferon alfa-2b in interferon treatment-naive patients with genotype 1, chronic hepatitis C. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1939.

S Pianko, EM Yoshida, S Zeuzem, and others. Health-related quality of life (HRQOL) with albinterferon alfa-2b plus ribavirin in IFN treatment-naive patients with genotype 1 chronic hepatitis C. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1939.