Ropeginterferon alfa-2b every 2 weeks as a novel pegylated interferon for patients with chronic hepatitis B

Abstract

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. Methods Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 μg (group 1), q2w 450 μg (group 2) or q1w PEG-IFN alfa-2a 180 μg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). Results The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 μg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). Conclusion In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B. Graphic abstract

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

“…Although PEG‐IFN was removed from current HCV treatment guidelines, ropeginterferon alfa‐2b is still the backbone of treatment for CHB or chronic hepatitis D (CHD), due to its antiviral mechanisms, which include direct inhibition of viral replication and the modulation of immune response. In our phase I/II study in CHB patients, ropeginterferon alfa‐2b showed comparable safety profile and better HBeAg seroconversion rate than PEG‐IFN alfa‐2a 2 . There are several approved treatments including PEG‐IFN, nucleoside analogues (lamivudine, entecavir, and telbivudine), and nucleotide analogues (adefovir dipivoxil, tenofovir disoproxil fumarate, and tenofovir alafenamide) in CHB.…”

“…However, increased pulmonary AEs were reported in the phase 3 trial and the project was discontinued in 2010 22 . In contrast, no lung toxicities was observed in ropeginterferon alfa‐2b use, up to totally 629 patients, including 102 healthy subjects, 313 patients with CHB or C, and 214 PV patients 1–3 …”

“… 22 In contrast, no lung toxicities was observed in ropeginterferon alfa‐2b use, up to totally 629 patients, including 102 healthy subjects, 313 patients with CHB or C, and 214 PV patients. 1 , 2 , 3 …”

“…The superior pharmacokinetics (PK) profile and longer half‐life of ropeginterferon alfa‐2b allow less frequent injections of once every 2 weeks. Moreover, ropeginterferon alfa‐2b dose up to 450 μg was safe and well‐tolerated in patients with genotype 2 chronic hepatitis C (CHC), PV, and chronic hepatitis B (CHB) 1–3 …”

“…Moreover, ropeginterferon alfa‐2b dose up to 450 μg was safe and well‐tolerated in patients with genotype 2 chronic hepatitis C (CHC), PV, and chronic hepatitis B (CHB). 1 , 2 , 3 …”