FDA Accepts Rusfertide NDA and Grants Priority Review for Polycythemia Vera Treatment
The FDA has accepted the New Drug Application for rusfertide, a first-in-class hepcidin mimetic peptide for polycythemia vera, and granted Priority Review with a PDUFA goal date in the third quarter of 2026.
Takeda and Protagonist Therapeutics announced that the U.S. Food and Drug Administration accepted the New Drug Application and granted Priority Review for rusfertide, an investigational first-in-class hepcidin mimetic peptide therapeutic for the treatment of adults with polycythemia vera. The FDA has set a Prescription Drug User Fee Act goal date in the third quarter of this calendar year.
The NDA submission was announced on January 5, 2026, seeking approval of rusfertide for the treatment of adults with polycythemia vera. Rusfertide is a first-in-class investigational subcutaneous treatment that mimics the action of hepcidin, a natural hormone that regulates iron homeostasis and red blood cell production. 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. Rusfertide is administered once weekly via subcutaneous self-injection.
In addition to Priority Review, rusfertide has received Breakthrough Therapy designation, Orphan Drug designation and Fast Track designation from the U.S. FDA. Breakthrough Therapy Designation is a regulatory milestone recognizing the potential of rusfertide to offer a substantial improvement over available therapies.
Polycythemia vera is characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, and can result in life threatening thrombotic events. Hematocrit is the ratio of red blood cells to the total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of less than 45% is the primary treatment goal in polycythemia vera to prevent thrombotic events and alleviate burdensome symptoms.
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, as well as four-year efficacy and safety data from the Phase 2 REVIVE study and long-term extension THRIVE study. In the VERIFY study, rusfertide met the primary endpoint and all four key secondary endpoints. Patients receiving rusfertide plus current standard of care demonstrated a higher response rate compared to current standard of care. This included hematocrit control, a reduction in phlebotomy requirements and improvement in pre-specified patient reported outcomes of fatigue and symptom burden. Patients receiving rusfertide plus standard of care therapy demonstrated a substantially higher response rate compared to placebo plus standard of care, including durable hematocrit control, a reduction in phlebotomy requirements and improvement in pre-specified patient reported outcome endpoints.
Rusfertide was generally well-tolerated through 52 weeks of treatment. The most common treatment-emergent adverse events in rusfertide-treated patients were injection site reactions (47.4%), anemia (25.6%) and fatigue (19.6%), which were mainly grade 1 or 2. Serious adverse events occurred in 8.1% of overall rusfertide-treated patients. Rusfertide has been generally well-tolerated in clinical trials to date.
The Phase 3 VERIFY study is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period, with treatment extension for participants who are continuing to derive benefit from rusfertide beyond the 156-week treatment period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include phlebotomy, hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during Weeks 20-32, which was defined as the absence of "phlebotomy eligibility." To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit of 45% or greater that was 3% or higher than their baseline hematocrit value, or hematocrit of 48% or greater.
In January 2024, Protagonist and Takeda entered into a worldwide license and collaboration agreement for rusfertide. Protagonist discovered rusfertide and led its development through Phase 3 studies, with Takeda responsible for implementing the regulatory strategy for the U.S. NDA filing and for leading any future global regulatory filings. Protagonist holds an option to co-commercialize in the U.S. through a 50/50 profit and loss share structure or to opt-out of this structure, providing Takeda with a worldwide license pursuant to the license and collaboration agreement.
Under the terms of the worldwide license and collaboration agreement, the submission of the NDA triggers the start of a 120-day period, after which Protagonist can decide to exercise its opt-out right during a subsequent 90-day period. If Protagonist chooses to exercise this opt-out right, it would be eligible to receive up to $400 million in opt-out payments as well as enhanced milestone payments and 14-29% tiered royalty rates on worldwide net sales of rusfertide.