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

doi:10.1002/jgh3.12613

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

JGH Open. 2021 Jul 10;5(8):929-940. doi: 10.1002/jgh3.12613. eCollection 2021 Aug.

Authors

Hsien-Hong Lin¹, Shih-Jer Hsu^{2

3}, Sheng-Nan Lu⁴, Wan-Long Chuang⁵, Chao-Wei Hsu⁶, Rong-Nan Chien⁶, Sien-Sing Yang⁷, Wei-Wen Su⁸, Jaw-Ching Wu⁹, Tzong-Hsi Lee¹⁰, Cheng-Yuan Peng¹¹, Kuan-Chiao Tseng¹², Albert Qin¹², Yi-Wen Huang^{13

14

15}, Pei-Jer Chen^{16

17}

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei Tzu Chi Hospital Taipei Taiwan.
² Department of Internal Medicine National Taiwan University Hospital Yunlin Branch Douliu and Huwei Taiwan.
³ Hepatology Medical Center, Department of Internal Medicine National Taiwan University Hospital Yunlin Branch Douliu Taiwan.
⁴ Division of Hepatogastroenterology, Department of Internal Medicine Chia-Yi Chang Gung Memorial Hospital Puzi Taiwan.
⁵ Department of Internal Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan.
⁶ Division of Hepatology, Department of Gastroenterology and Hepatology Linkou Medical Center, Chang Gung Memorial Hospital Taoyuan Taiwan.
⁷ Liver Center, Department of Internal Medicine Cathay General Hospital Medical Center Taipei Taiwan.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan.
⁹ Medical Research Department Taipei Veterans General Hospital Taipei Taiwan.
¹⁰ Division Gastroenterology, Department of Internal Medicine Far-Eastern Memorial Hospital New Taipei City Taiwan.
¹¹ Center for Digestive Medicine, Department of Internal Medicine China Medical University Hospital, and School of Medicine, China Medical University Taichung Taiwan.
¹² Department of Medical Research PharmaEssentia Corp Taipei Taiwan.
¹³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University Taipei Taiwan.
¹⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan.
¹⁵ Department of Internal Medicine, School of Medicine National Taiwan University College of Medicine Taipei Taiwan.
¹⁶ Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan.
¹⁷ Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan.

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 (AUC_0-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.