Ropeginterferon alfa-2b in patients with genotype 1 chronic hepatitis C: Pharmacokinetics, safety, and preliminary efficacy

Hsien-Hong Lin, Shih-Jer Hsu, Sheng-Nan Lu, Wan-Long Chuang, Chao-Wei Hsu, Rong-Nan Chien, Sien-Sing Yang, Wei-Wen Su, Jaw-Ching Wu, Tzong-Hsi Lee, Cheng-Yuan Peng, Kuan-Chiao Tseng, Albert Qin, Yi-Wen Huang, Pei-Jer Chen, Hsien-Hong Lin, Shih-Jer Hsu, Sheng-Nan Lu, Wan-Long Chuang, Chao-Wei Hsu, Rong-Nan Chien, Sien-Sing Yang, Wei-Wen Su, Jaw-Ching Wu, Tzong-Hsi Lee, Cheng-Yuan Peng, Kuan-Chiao Tseng, Albert Qin, Yi-Wen Huang, Pei-Jer Chen

Abstract

Background and aim: Ropeginterferon alfa-2b (P1101) is a novel long-acting mono-PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N-terminus, allowing every-two-week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa-2b as compared with PEG-IFN-α2a in patients with chronic hepatitis C virus genotype 1 infection.

Methods: One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG-IFN-α2a 180 μg (group 1), weekly ropeginterferon alfa-2b 180 μg (group 2), weekly ropeginterferon alfa-2b 270 μg (group 3), or biweekly ropeginterferon alfa-2b 450 μg (group 4) plus ribavirin for 48 weeks.

Results: After multiple weekly administration, serum exposure (AUC0-τ) in ropeginterferon alfa-2b 180 μg was approximately 41% greater and the accumulation ratio of 2-fold greater than PEG-IFN-α2a 180 μg. The incidences of flu-like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1-4, respectively. Two grade 2 of 3 depression were noted in PEG-IFN-α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively.

Conclusions: Ropeginterferon alfa-2b showed longer effective half-life and superior safety profile than PEG-IFN-α2a. Biweekly injection of ropeginterferon alfa-2b will be studied in larger viral hepatitis patient population.

Keywords: antiviral; chronic hepatitis C; clinical trial; genotype 1; interferon; ropeginterferon alfa‐2b.

© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Figures

Figure 1
Figure 1
(a) Drug concentration of P1101/Pegasys across treatment week (safety population). Group 1: PEG‐IFN‐α2a 180 μg QW; group 2: ropeginterferon alfa‐2b 180 μg QW; group 3: ropeginterferon alfa‐2b 270 μg QW; group 4: ropeginterferon alfa‐2b 450 μg Q2W. Group 3 had the highest mean serum concentrations from TW3 to TW48, almost twice the mean serum concentration of the other three groups. After TW48, the drug concentrations of all treatment groups declined to undetectable levels. (b) Drug concentration of ribavirin across treatment week (safety population). Group 1: PEG‐IFN‐α2a 180 μg QW; group 2: ropeginterferon alfa‐2b 180 μg QW; group 3: ropeginterferon alfa‐2b 270 μg QW; group 4: ropeginterferon alfa‐2b 450 μg Q2W. The mean concentrations of ribavirin for all treatment groups showed similar trends at all study time points. PEG‐IFN, pegylated interferon.
Figure 2
Figure 2
(a) Mean serum drug concentration–time profiles (after first dose). Group 1: PEG‐IFN‐α2a 180 μg QW; group 2: ropeginterferon alfa‐2b 180 μg QW; group 3: ropeginterferon alfa‐2b 270 μg QW; group 4: ropeginterferon alfa‐2b 450 μg Q2W. Single (first dose) and multiple dose (last dose) serum concentration–time plots by group. (b) Mean serum drug concentration–time profiles (after last dose). Group 1: PEG‐IFN‐α2a 180 μg QW; group 2: ropeginterferon alfa‐2b 180 μg QW; group 3: ropeginterferon alfa‐2b 270 μg QW; group 4: ropeginterferon alfa‐2b 450 μg Q2W. Single (first dose) and multiple dose (last dose) serum concentration–time plots by group. PEG‐IFN, pegylated interferon.
Figure 3
Figure 3
Cumulative incidence of flu‐like symptoms (safety population). Group 1: PEG‐IFN‐α2a 180 μg QW; group 2: ropeginterferon alfa‐2b 180 μg QW; group 3: ropeginterferon alfa‐2b 270 μg QW; group 4: ropeginterferon alfa‐2b 450 μg Q2W; In the analysis of the flu‐like symptoms, the MedDRA preferred term arthralgia, myalgia, pyrexia, chills, headache, and influenza like illness were added for analysis. PEG‐IFN, pegylated interferon.

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