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
Affiliations
Hsien‐Hong Lin
Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei Tzu Chi Hospital Taipei Taiwan
Shih‐Jer Hsu
Department of Internal Medicine National Taiwan University Hospital Yunlin Branch Douliu and Huwei Taiwan
Sheng‐Nan Lu
Division of Hepatogastroenterology, Department of Internal Medicine Chia‐Yi Chang Gung Memorial Hospital Puzi Taiwan
Wan‐Long Chuang
Department of Internal Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan
Chao‐Wei Hsu
Division of Hepatology, Department of Gastroenterology and Hepatology Linkou Medical Center, Chang Gung Memorial Hospital Taoyuan Taiwan
Rong‐Nan Chien
Division of Hepatology, Department of Gastroenterology and Hepatology Linkou Medical Center, Chang Gung Memorial Hospital Taoyuan Taiwan
Sien‐Sing Yang
Liver Center, Department of Internal Medicine Cathay General Hospital Medical Center Taipei Taiwan
Wei‐Wen Su
Division of Gastroenterology and Hepatology, Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan
Jaw‐Ching Wu
Medical Research Department Taipei Veterans General Hospital Taipei Taiwan
Tzong‐Hsi Lee
Division Gastroenterology, Department of Internal Medicine Far‐Eastern Memorial Hospital New Taipei City Taiwan
Cheng‐Yuan Peng
Center for Digestive Medicine, Department of Internal Medicine China Medical University Hospital, and School of Medicine, China Medical University Taichung Taiwan
Kuan‐Chiao Tseng
Department of Medical Research PharmaEssentia Corp Taipei Taiwan
Albert Qin
Department of Medical Research PharmaEssentia Corp Taipei Taiwan
Yi‐Wen Huang
Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University Taipei Taiwan
Pei‐Jer Chen
Graduate Institute of Clinical Medicine National Taiwan University College of Medicine 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 (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.
