FDA Accepts New Drug Application for Rusfertide, Grants Priority Review In Polycythemia Vera

Rusfertide, as a potential first-in-class therapy for polycythemia vera (PV), had its New Drug Application (NDA) accepted and Priority Review granted by the US Food and Drug Administration (FDA).1

The results were announced by Takeda and Protagonist on March 2, 2026, based on results from the phase 3 VERIFY, phase 2 REVIEW, and long-term extension THRIVE study, with the Prescription Drug User Fee Act (PDUFA) target action date set for the third quarter of this calendar year.1

PV is a rare, slow-growing blood cancer where bone marrow overproduces red blood cells, causing hyperviscosity, along with secondary white blood cell and platelet production. The myeloproliferative disorder is associated with a Janus kinase-2 (JAK2) mutation, which causes the neoplastic proliferation of the hematopoietic progenitor cells. The primary treatment goal for PV is to control hematocrit levels <45% to prevent thrombotic events and alleviate burdensome symptoms.1,2

Previously, rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic for the treatment of adults with PV, already received designation for Breakthrough Therapy, Orphan Drug, and Fast Track from the Agency. By targeting the underlying mechanism of iron dysregulation in polycythemia vera, rusfertide aims to reduce excess red blood cell production and help patients achieve sustained hematocrit control.1

“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,” said Andy Plump, MD, PhD, president of R&D at Takeda in a statement. “The FDA's acceptance of our NDA brings us closer to potentially offering a first-in-class therapy that could meaningfully improve clinical outcomes and quality of life. This milestone is a reflection of our successful partnership with Protagonist and Takeda’s unwavering commitment to advancing innovative treatments in hematologic cancers where significant unmet needs persist.”1

According to the release, the NDA for rusfertide was based primarily on positive 32-week primary analysis and 52-week results from the global, randomized, phase 3 VERIFY study, as well as 4-year efficacy and safety data from phase 2 REVIEW and long-term extension THRIVE.1

The primary endpoint of VERIFY was the proportion of patients who achieved a response during Weeks 20-32, defined as the absence of “phlebotomy eligibility.” To meet phlebotomy eligibility, patients in the study were required to have a confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or a hematocrit ≥48%.1

In VERIFY, rusfertide met the primary endpoint and all 4 key secondary endpoints, and compared to receiving the current standard of care alone, patients receiving rusfertide plus the current standard of care demonstrated an increased response rate. Among these results were hematocrit control, a reduction in phlebotomy requirements, and improvement in pre-specified patient-reported outcomes of fatigue and symptom burden.1

Over 52 weeks of treatment, rusfertide was generally well-tolerated. The most common treatment-emergent adverse events (AEs) in rusfertide-treated patients were injection site reactions (47.4%), anemia (25.6%), and fatigue (19.6%), a majority of which were grade 1 or 2. Of rusfertide-treated patients, serious AEs occurred in 8.1% of individuals.1

After completing their participation in the randomized, placebo-controlled portion of the study, all patients are now in the open-label portions of the study.1

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. BusinessWire. Published March 2, 2026. Accessed March 2, 2026. https://www.businesswire.com/news/home/20260301580219/en/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

2. Lu X, Chang R. Polycythemia Vera. PubMed. Published April 24, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557660/

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