Management of polycythemia vera (PV) rests on phlebotomy and low-dose aspirin, with cytoreduction (traditionally hydroxyurea) for higher-risk patients — but the options for disease control have expanded meaningfully. Ropeginterferon alfa-2b (Besremi), approved in 2021, was the first interferon licensed specifically for PV; beyond controlling blood counts it can induce molecular responses and may modify the disease course, and it is increasingly used earlier.
The most novel development is rusfertide, a hepcidin mimetic that controls erythrocytosis by restricting the iron availability that red-cell production depends on — effectively a pharmacological alternative to repeated phlebotomy. In the Phase 2 REVIVE trial it cut phlebotomy requirements dramatically, and the Phase 3 VERIFY trial (2025) confirmed the benefit, with about 77% of rusfertide-treated patients achieving a clinical response versus 33% on placebo, plus improvements in fatigue and symptom burden. Rusfertide is now under FDA priority review, with a decision anticipated in 2026; injection-site reactions are the most common side effect. For hydroxyurea-resistant or -intolerant patients, ruxolitinib remains an established option, and further agents (such as the siRNA divesiran) are in development.
Further reading: rusfertide REVIVE (Kremyanskaya et al., NEJM 2024) and Phase 3 VERIFY (2025); ropeginterferon alfa-2b in PV; ruxolitinib RESPONSE.