Takeda  and Protagonist Therapeutics, Inc. (“Protagonist”)  announced that the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) and granted Priority Review for rusfertide. Rusfertide is an investigational, first-in-class hepcidin mimetic peptide therapeutic for the treatment of adults with polycythemia vera (PV). The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date in the third quarter of this calendar year. In addition to Priority Review, rusfertide has received Breakthrough Therapy designation, Orphan Drug designation and Fast Track designation from the U.S. FDA.

PV 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 <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate burdensome symptoms.

“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, M.D., Ph.D., president of R&D at Takeda. “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.”

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), as well as four-year efficacy and safety data from the Phase 2 REVIVE study (NCT04057040) and long-term extension THRIVE study (NCT06033586). 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. Rusfertide was generally well-tolerated through 52 weeks of treatment. 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%), which were mainly grade 1 or 2. Serious AEs occurred in 8.1% of overall rusfertide-treated patients.

“Rusfertide exemplifies Protagonist’s end-to-end expertise, from exploring a novel hepcidin mimetic mechanism to address unmet needs in polycythemia vera to discovering the peptide and driving its clinical development through NDA filing. We are very pleased with the FDA granting rusfertide Priority Review and look forward to its potential approval in 2026,” said Dinesh V. Patel, Ph.D., Protagonist President and CEO. “We have identified a great partner in Takeda as rusfertide progresses toward this milestone, thereby bringing a successful closure to our more than decade-long journey from concept-to-commercialization.”

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.