Ropeginterferon alfa-2b, a novel mono-pegylated interferon alfa-2b, has demonstrated promising efficacy and safety in treating polycythemia vera (PV) patients, according to a phase 1/2 clinical study. The study, involving 51 PV patients, showed a high overall response rate and significant molecular responses, suggesting the drug's potential as a long-term treatment option.
Study Design and Patient Population
The multicenter, open-label, dose-escalation study evaluated ropeginterferon alfa-2b in patients with confirmed PV, including newly diagnosed, pretreated, and hydroxyurea (HU)-exposed individuals. The trial's phase 1 portion aimed to define the maximum tolerated dose (MTD), while phase 2 focused on hematologic and molecular responses. Ropeginterferon alfa-2b was administered subcutaneously every 14 days, with doses ranging from 50 to 540 μg. The median follow-up duration was 80 weeks.
Hematologic Response
The study reported an overall hematologic response rate of 82% at 1 year, with 29% of patients achieving complete response (CR). The best individual response rate reached 90%, comprising 47% CR and 43% partial response (PR). Treatment with ropeginterferon alfa-2b stabilized hematocrit levels, with 74% of evaluated patients achieving hematocrit levels below 45% and remaining phlebotomy-free by 12 months. Platelet and white blood cell counts also decreased substantially.
Molecular Response
Significant reductions in JAK2 V617F allelic burden were observed during the study. The median JAK2 V617F allelic burden decreased from 41% at study entry to 25% by week 50 (P < .001). The cumulative molecular response rate at week 114 was 78%. Patients with complete hematologic response had a significantly higher likelihood of achieving a molecular response (OR = 2.8; 95% CI, 1.6-4.7; P < .001).
Safety and Tolerability
No dose-limiting toxicities were observed, and the MTD was defined as the highest dose evaluated (540 μg). All drug-related adverse events were known toxicities associated with IFN-α. The favorable safety profile of ropeginterferon alfa-2b, along with its bi-weekly administration, may improve patient compliance and long-term tolerability.
Clinical Implications
Polycythemia vera is a myeloproliferative neoplasm characterized by increased red blood cell mass and a risk of thromboembolic complications. While interferon alfa (IFN-α) has shown efficacy in normalizing blood cell counts and preventing complications, its clinical use has been limited by poor tolerance. Ropeginterferon alfa-2b, with its improved tolerability and longer half-life, represents a promising therapeutic option for PV patients. The study findings support the continued development of ropeginterferon alfa-2b in randomized phase 3 clinical trials to further evaluate its efficacy and safety.
