FDA Accepts NDA, Assigns Priority Review for Rusfertide in PV

The FDA has accepted the New Drug Application (NDA) and granted priority review for rusfertide, a first-in-class hepcidin mimetic peptide therapeutic for adults with polycythemia vera (PV), with a Prescription Drug User Fee Act (PDUFA) goal date set for the third quarter of this calendar year.¹

The NDA for rusfertide was primarily based on the positive 32-week primary analysis and 52-week results from the phase 3 global randomized VERIFY study (NCT05210790),² as well as efficacy and safety data from the phase 2 REVIVE study (NCT04057040) and long-term extension THRIVE study (NCT06033586).

Efficacy and Safety Results

The phase 3 VERIFY study is an ongoing, 3-part, global, randomized, placebo-controlled trial enrolling 293 patients with PV over a 156-week treatment period, with an extension for participants continuing to derive benefit beyond that window. The study evaluates once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who remain phlebotomy-dependent despite current standard of care, which may include phlebotomy, hydroxyurea (Hydrea), interferon, and/or ruxolitinib (Jakafi).

The primary end point was the proportion of patients achieving a response during weeks 20 to 32, defined as the absence of phlebotomy eligibility. Phlebotomy eligibility was met if a patient had a confirmed hematocrit of 45% or greater that was at least 3% above their baseline value, or a hematocrit greater than 48%. All patients have since completed the randomized, placebo-controlled portion of the study and are now participating in the open-label phases.

All patients have completed their participation in the randomized, placebo-controlled portion of the study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study.

“There is an urgent need for innovative treatment options in polycythemia vera, where patients currently face limited therapeutic choices to control their hematocrit and significant symptom burden,” Andy Plump, MD, PhD, president of research and development at Takeda, said.

About REVIVE and THRIVE

The phase 2 REVIVE study³ evaluated rusfertide in adult patients with PV and consisted of 3 parts, including 70 patients in the dose-finding part 1 (28 weeks), 59 patients in the blinded, placebo-controlled, randomized withdrawal part 2 (13 weeks) and 58 patients in the part 3 open-label expansion (52 weeks).

The THRIVE study⁴ is an ongoing, open-label extension study evaluating the long-term durability of response and safety profile of rusfertide in patients with PV. The study includes 46 patients who previously participated in REVIVE. Patients eligible to transition to the THRIVE study completed the open-label extension portion of REVIVE, 12 months or more of rusfertide therapy and had an end-of-treatment visit. THRIVE is designed to further assess the maintenance of hematocrit control, reduction in the need for therapeutic phlebotomy and overall safety of once-weekly, subcutaneous rusfertide over an additional 2-year treatment period.

REFERENCES

1. Takeda and Protagonist Announce U.S. Food and Drug Administration Accepts New Drug Application and Grants Priority Review for Rusfertide as a Potential First-in-Class Therapy for Polycythemia Vera. News release. March 2, 2026. Accessed March 5, 2026. https://www.takeda.com/newsroom/newsreleases/2026/nda-rusfertide/

2. 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;43(suppl 17):LBA3. doi: 10.1200/JCO.2025.43.17_suppl.LBA3

3. 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;144(suppl 1):4559. doi:10.1182/blood-2024-197985

4. 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;146(suppl 1):3810. doi: 10.1182/blood-2025-3810