Ropeginterferon alfa-2b 250micrograms/0.5ml solution for injection pre-filled disposable devices

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by increased red blood cell production, with high risk of venous and arterial thrombosis. Mutations in the JAK2 gene, particularly JAK2 V617F, play a central role in its pathogenesis. Ropeginterferon alfa-2b is a novel long-acting interferon showing promise in managing PV through hematologic and molecular control.This study aimed to evaluate the efficacy and safety of Ropeginterferon alfa-2b in patients with PV based on a systematic review and meta-analysis of available clinical trials.A systematic search was conducted across PubMed, Cochrane Library, Web of Science, Google Scholar, and Scopus on May 8, 2025. Randomized controlled trials (RCTs) assessing Ropeginterferon alfa-2b in PV were included. The PRISMA guidelines were followed, and the protocol was registered in PROSPERO (CRD420251051466). Quality assessment was performed using RoB 2.0 and ROBINS-I tools. A random-effects model was applied using R software.Eight studies involving 761 patients were included and only six studies included in single arm meta-analysis with 328 patients. The pooled proportion of complete hematological response at 12 months was 0.63 (95% CI [0.51-0.73]), with high heterogeneity. Reductions in JAK2 V617F allele burden were significant (MD: 26.57, 95% CI [13.49-39.65]). Molecular response was achieved in 25% (95% CI [0.04-0.70]) of patients. The most common adverse events were elevated liver enzymes (AST: 0.28; ALT: 0.32), influenza-like illness (0.11), and anemia (0.09), with unresolved heterogeneity in all outcomes.Ropeginterferon alfa-2b shows promising efficacy in achieving hematological and molecular responses in patients with PV. However, notable heterogeneity and safety concerns, particularly liver-related adverse effects, warrant further investigation in large-scale trials.

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Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.

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Interferon alfa not only restores normal blood cell counts in patients with polycythemia vera (PV) but can diminish the mutant JAK2V617F allele burden After discontinuing long-term interferon therapy, hematologic responses may persist Allele burden declines gradually during interferon treatment

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Ropeginterferon alfa-2b is a novel, long-acting mono-pegylated proline-IFN-alpha-2b approved for treatment of polycythemia vera in adults, regardless of thrombotic risk level or treatment history. Clinical trial data indicate the dose and titration of ropeginterferon alfa-2b is safe and effective. However, additional studies may provide rationale for an amended, higher initial dosage and rapid titration. This article is an overview of current and upcoming studies of ropeginterferon alfa-2b in myeloproliferative neoplasms that support the exploration of an amended dosing scheme in order to optimize patient tolerability and efficacy outcomes.

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Abstract Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2–4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250–350–500 μg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2 V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250–350–500 μg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses. Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

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Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2 V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2 V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2 V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm 2 at baseline to 50.2 cm 2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option. J Hematol. 2024;13(1-2):12-22 doi: https://doi.org/10.14740/jh1245

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