Three-step dose escalation of ropeginterferon alfa‑2b in PV: A Japanese phase IIIb study

Results from the phase IIIb, open-label, single-arm, multicenter study (NCT06002490), evaluating a three-step dose escalation regimen of ropeginterferon alfa‑2b (250 µg on Day 1, 350 µg at Week 2, 500 µg at Week 4) in 21 Japanese patients with polycythemia vera (PV), were published by Inano et al. in the International Journal of Hematology. The primary efficacy endpoint was rate of 12-week phlebotomy-free complete hematologic response (CHR), defined as hematocrit <45% without phlebotomy in the previous 12 weeks, platelet count ≤400 × 10⁹/L, and white blood cell count ≤10 × 10⁹/L, at Week 24. Safety endpoints included treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs). 

Key data: A CHR was demonstrated by 23.8% of patients at Week 12 (95% confidence interval [CI], 8.2–47.2) and 57.1% of patients at Week 24 (95% CI, 34.0–78.2). The median time to CHR was 18.14 weeks. The median time to first response in peripheral blood count was 4.14 weeks for platelets, 2.14 weeks for white blood cells, and 0.14 weeks for hematocrit. Most study participants (90.5%) reached the maximum dose of 500 µg by Week 4. All patients experienced at least one TEAE, including TRAEs. Grade 3 TEAEs occurred in 9.5% of patients, none of which were considered to be treatment related. 

Key learning: A three-step dose escalation regimen of ropeginterferon alfa‑2b achieved a CHR in over half of Japanese patients with PV within 24 weeks, with no new safety concerns identified, suggesting that this approach may provide faster therapeutic effects compared with the standard slow titration regimen used in Japan.