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

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.

Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

“…In further clinical development, ropeginterferon alfa‐2b has been evaluated for the safety and efficacy for the treatment of HCV genotypes 1 and 2, 39,40 HBV 41 and polycythaemia vera 13–20,42,43 . Results of clinical trials in viral hepatitis showed that ropeginterferon alfa‐2b is as safe and effective as pegylated IFN alfa‐2a for the treatment of hepatitis B and C‐infected patients.…”

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan

“…For the treatment of polycythemia vera , which is a chronic myeloproliferative neoplasm, long-term and continuous treatment subcutaneously once every 2 weeks with ropeginterferon alfa-2b led to impressive hematological and clinical responses and was generally well tolerated [ 24 ]. Antiviral efficacy and good tolerability of ropeginterferon alfa-2b for the treatment of chronic HBV or HCV infections have also been demonstrated in several clinical studies [ 16 , 19 , 20 ]. Here, we report for the first time that a single subcutaneous administration of ropeginterferon alfa-2b showed promising clinical effect on COVID-19 patients with moderate disease, especially in younger patients who are ≤ 65 years old.…”

Novel Pegylated Interferon for the Treatment of Chronic Viral Hepatitis

“…By contrast, ropeginterferon alfa-2b showed a favorable dosing schedule and safety profile in the treatment of chronic hepatitis including CHC and CHB. Two phase 2 clinical studies have been conducted to explore and validate the safety and efficacy of ropeginterferon alfa-2b in combination with ribavirin in the CHC treatment, including one in CHC genotype 1 and the other in CHC genotype 2 (Table 2) [10,11]. Abbreviation: CHC: chronic hepatitis C; SVR12: sustained virologic response at 12 weeks post-treatment; SVR12: sustained virologic response at 24 weeks post-treatment.…”

“…In the phase 2 CHC genotype 1 study [10], 106 treatment naive patients were enrolled and randomized into four treatment groups including peginterferon alfa-2a once every week SC at the dose of 180 µg (Group 1) as a control, ropeginterferon alfa-2b SC once every week at 180 or 270 µg (Group 2 and Group 3, respectively) or once every two weeks at 450 µg (Group 4), plus daily oral ribavirin for a treatment of 48 weeks [10]. Patients who were treated with ropeginterferon alfa-2b at 180 µg showed a notably higher serum exposure (AUC 0-τ ), which was 1.4-fold greater than those treated with peginterferon alfa-2a at the same dose.…”

“…Another major application of IFN alfa (alpha) is for the treatment of chronic viral hepatitis, such as hepatitis B, C, and D. To identify the clinical values of ropeginterferon alfa-2b in these clinical indications, ropeginterferon alfa-2b has been evaluated in phase 1 and 2 clinical trials for the treatment of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) [10][11][12]. We summarized the relevant clinical results to show that ropeginterferon alfa-2b as a novel IFN alfa-based therapy was well tolerated and effective in these clinical studies and discuss the future perspectives in using ropeginterferon alfa-2b for the treatment of chronic viral hepatitis.…”