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FDA approves rusfertide as a first-in-class therapy for the treatment of polycythemia vera

On August 28, 2026, the U.S. Food and Drug Administration (FDA) granted approval to rusfertide for the treatment of adult patients with polycythemia vera (PV).1

PV is a rare, slow-growing myeloproliferative neoplasm (MPN) characterized by excess red blood cell production, which results in an increased risk of thromboembolic events.2 Currently approved therapies for PV aim to lower thrombotic risk and disease related symptoms by reducing hematocrit levels to <45%, however effective treatment options remain limited.2 

Rusfertide is a first-in-class synthetic hepcidin mimetic designed to reduce hematocrit levels by binding to ferroportin to block intracellular iron export, thereby reducing serum iron levels and limiting red blood cell production.2

The FDA approval of rusfertide is primarily based on data from the Phase III VERIFY trial (NCT05210790).1 This double-blind, placebo (PBO)-controlled study enrolled 293 patients with PV who were randomized 1:1 to receive once-weekly, subcutaneously self-administered rusfertide (n=147) or PBO (n=146).3  The trial met its primary endpoint, with a significantly higher proportion of rusfertide-treated patients achieving a clinical response, defined as an absence of phlebotomy eligibility and no phlebotomies from Weeks 20–32, compared with patients on PBO (76.9% versus 32.9%, respectively; p<0.0001).3 Key secondary endpoints were also met, with rusfertide treatment leading to a reduction in the mean number of phlebotomies over 32 weeks of treatment (0.5 for rusfertide versus 1.8 for PBO; p<0.0001) and an increase in the proportion of patients maintaining a hematocrit level of <45% (62.6% in the rusfertide arm versus 14.4% with PBO; p<0.0001). 3 Patients in the treatment arm also demonstrated improvements in patient-reported outcomes, including fatigue and symptom burden scores (PROMIS Fatigue Short Form 8a total T-score and the MFSAF v4.0 Total Symptom Score; p<0.03).3

The most common adverse events in the treatment arm were injection-site reactions (55.9% versus 32.9% with PBO), followed by anemia (15.9%) and fatigue (15.2%), while serious adverse events were infrequent (3.4%) and not considered related to rusfertide.3

Long-term follow-up data from the Phase II REVIVE trial (NCT04057040) and the Phase II THRIVE extension study (NCT06033586) further support the sustained efficacy and safety of rusfertide in PV.4, 5 Patients who completed the REVIVE open-label extension were eligible to transition to THRIVE, which continues to assess the durability of hematocrit control, phlebotomy requirements, and long-term safety outcomes with rusfertide therapy for a total of up to 5.8 years. Findings to date demonstrate sustained responses, with maintained reductions in phlebotomy burden and a consistent long-term safety profile.4, 5  

In an interview earlier this year, Andrew Kuykendall, MD, from Moffitt Cancer Center, Tampa, FL, discussed where rusfertide may fit in the treatment algorithm for PV following it’s approval, highlighting that the agent “could be a part of everyone’s journey with polycythemia vera.” Dr Kuykendall states: “I think it’s easiest to see in those patients that are requiring frequent phlebotomy or don’t tolerate phlebotomy or are challenged by the frequent visits to the doctor’s office and getting the lab checks that come with phlebotomy.”

The approval of rusfertide represents a significant advance in PV treatment, providing patients with a first-in-class, non-cytoreductive therapy that achieves durable hematocrit control, decreases phlebotomy requirements, and reduces symptom burden.

For further insights into the role of rusfertide and other hepcidin-modulating agents in PV, including expert perspectives on their clinical potential, read our recently published feature article here.

References

  1. U.S. Food and Drug Administration. FDA Approves First Drug of Its Kind for Polycythemia Vera, a Rare Blood Disorder. Available here. (Last accessed 29/08/2026).
  2. Kremyanskaya M, Kuykendall AT, Pemmaraju N, et al. Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera. N Engl J Med. 2024 Feb;390(8):723-735.
  3. Kuykendall AT, Pemmaraju N, Pettit KM, et al. Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). J Clin Oncol. 2025 Jun;43(17).
  4. Gerds AT, Kuykendall AT, Kremyanskaya M, et al. Final Results from the Phase 2 Revive Study Investigating the Hepcidin Mimetic Rusfertide in Patients with Polycythemia Vera (PV). Blood. 2024 Nov;144(1): 4559.
  5. Pemmaraju N, Kuykendall A, Ritchie E, et al. Long-term rusfertide treatment in polycythemia vera: Initial results from the phase 2 THRIVE extension study. Blood. 2025 Nov;146 (1): 3810.

Written by Clare Harris

Edited by Natalie Markova