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.
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Source: PubMed