FDA Grants Priority Review to Takeda’s Rusfertide for Polycythemia Vera

Takeda and Protagonist Therapeutics announced that the U.S. FDA has accepted the New Drug Application (NDA) for Rusfertide, an investigational first-in-class hepcidin mimetic peptide for adults with Polycythemia vera (PV). The agency granted Priority Review, setting a PDUFA goal date in the third quarter of 2026. Rusfertide also holds Breakthrough Therapy, Orphan Drug, and Fast Track designations.

Takeda submitted the NDA for rusfertide in January 2026.

PV involves overproduction of red blood cells (erythrocytosis), raising blood viscosity and thrombotic risks like stroke or embolism. Controlling hematocrit below 45% is the core treatment goal to curb these events and ease symptoms such as fatigue, poor concentration, night sweats, and pruritus.

Andy Plump, M.D., Ph.D., Takeda’s President of R&D, highlighted the unmet need: “Patients face limited options for hematocrit control and symptom relief. This NDA acceptance advances a potential first-in-class therapy via our partnership with Protagonist.”

The NDA draws primarily from the Phase 3 VERIFY study (NCT05210790), which met its primary endpoint and all four key secondary endpoints at 32 and 52 weeks. Rusfertide plus standard of care (e.g., phlebotomy, hydroxyurea, interferon, ruxolitinib) outperformed standard care alone in response rates, hematocrit control, phlebotomy reduction, and patient-reported fatigue/symptom improvements among 293 phlebotomy-dependent patients. Rusfertide was well-tolerated; common adverse events included injection site reactions (47.4%), anemia (25.6%), and fatigue (19.6%), mostly grade 1/2, with serious events in 8.1%.

Supporting data come from the Phase 2 REVIVE study (NCT04057040) including dose-finding, randomized withdrawal, and open-label phases and the ongoing THRIVE extension (NCT06033586), showing four-year efficacy and safety.

Rusfertide, discovered by Protagonist, mimics hepcidin to regulate iron and curb excess red blood cell production. It’s a once-weekly subcutaneous self-injection. Protagonist led development through Phase 3; Takeda handles U.S. regulatory strategy and global filings under their January 2024 worldwide license agreement. Protagonist retains a U.S. co-commercialization option (50/50 profit/loss share).

Dinesh V. Patel, Ph.D., Protagonist’s President and CEO, noted: “This Priority Review caps our decade-long journey from concept to NDA, with Takeda as an ideal partner.”

All VERIFY patients have completed the randomized phase and entered open-label extensions. REVIVE-THRIVE data reinforce long-term hematocrit control and phlebotomy reduction.

This milestone signals progress for PV management, potentially transforming care for uncontrolled patients.

 References

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, 02 March 2026, FDA Accepts NDA and Grants Priority Review for Rusfertide

Breakthrough Rusfertide Phase 3 VERIFY Results: 52-Week Hematocrit Control and PRO Improvements in PV at ASH 2025, 08 December 2025, https://pharmacally.com/breakthrough-rusfertide-phase-3-verify-results-52-week-hematocrit-control-and-pro-improvements-in-pv-at-ash-2025/

A Phase 3 Study of Rusfertide in Patients with Polycythemia Vera (VERIFY), ClinicalTrials.gov ID NCT05210790, https://clinicaltrials.gov/study/NCT05210790

Hepcidin Mimetic in Patients with Polycythemia Vera (REVIVE), ClinicalTrials.gov ID NCT04057040, https://clinicaltrials.gov/study/NCT04057040

Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects with Polycythemia Vera (THRIVE), ClinicalTrials.gov ID NCT06033586, https://clinicaltrials.gov/study/NCT06033586