CAMBRIDGE, Mass.– Takeda and Protagonist Therapeutics announced that the U.S. Food and Drug Administration has accepted the New Drug Application for rusfertide and granted the investigational therapy Priority Review for the treatment of adults with polycythemia vera (PV).
Rusfertide is described as a first-in-class hepcidin mimetic peptide designed to address iron dysregulation and excess red blood cell production in PV. The FDA has set a Prescription Drug User Fee Act target action 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 agency.
Polycythemia vera is marked by overproduction of red blood cells, which increases blood viscosity and raises the risk of life-threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. Maintaining hematocrit levels below 45% is the primary treatment goal to reduce these risks and ease symptoms including fatigue, difficulty concentrating, night sweats and pruritus.
“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 submission is primarily supported by data from the Phase 3 VERIFY study, which evaluated rusfertide in combination with standard of care. In the 32-week primary analysis and 52-week results, rusfertide met the primary endpoint and all four key secondary endpoints. Patients receiving rusfertide plus current standard of care demonstrated higher response rates compared with standard of care alone, including improved hematocrit control, reduced need for phlebotomy and improvements in pre-specified patient-reported outcomes related to fatigue and symptom burden.
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 rusfertide-treated patients.
Longer-term data from the Phase 2 REVIVE study and its extension study, THRIVE, provided up to four years of efficacy and safety follow-up and were also included in the NDA package.
“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 led development of the therapy through Phase 3, while Takeda is responsible for U.S. regulatory strategy and any future global regulatory filings. Protagonist retains an option to co-commercialize the product in the United States under a 50/50 profit-and-loss share arrangement or to opt out in exchange for granting Takeda a worldwide license under the collaboration agreement.
Rusfertide is administered once weekly via subcutaneous self-injection and is designed to mimic the action of hepcidin, a natural hormone that regulates iron homeostasis and red blood cell production.
