Takeda and Protagonist File NDA for Rusfertide in Polycythemia Vera
Takeda Pharmaceutical Company Limited and Protagonist Therapeutics, Inc. have announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for rusfertide, an investigational therapy intended for the treatment of adults with polycythemia vera (PV).Rusfertide is a first-in-class, subcutaneously administered hepcidin mimetic peptide designed to regulate iron metabolism and red blood cell production. By targeting iron homeostasis, the therapy aims to maintain hematocrit levels and address the underlying causes of erythrocytosis in patients with PV.
Commenting on the milestone, Teresa Bitetti, President of Takeda’s Global Oncology Business Unit, highlighted the unmet needs faced by patients living with PV. She noted that data generated from the VERIFY clinical program demonstrate rusfertide’s potential to deliver durable hematocrit control while reducing the reliance on phlebotomy and easing symptom burden. Bitetti also emphasized the value of Takeda’s collaboration with Protagonist in advancing innovative treatments that can meaningfully improve patient care.
The NDA submission is supported by results from the Phase 3 VERIFY study (NCT05210790), a global randomized, placebo-controlled trial. In both the 32-week primary analysis and the 52-week follow-up, rusfertide achieved the primary endpoint along with all four key secondary endpoints. Patients treated with rusfertide in combination with standard of care showed significantly higher response rates compared with placebo, including sustained hematocrit control, fewer phlebotomy procedures, and improvements in pre-specified patient-reported outcomes. Additional supportive evidence was generated from the Phase 2 REVIVE study (NCT04057040).
Rusfertide has also received several regulatory designations from the FDA, including Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation, reflecting its potential to offer meaningful advantages over existing treatment options for PV.
Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist Therapeutics, stated that rusfertide could represent a significant shift in the management of PV by providing a targeted, erythrocytosis-specific therapy. He noted that the NDA submission marks a major milestone in the company’s long-term development efforts and underscores rusfertide’s potential to become a new standard of care for patients who currently depend on frequent and burdensome phlebotomy.
Under the worldwide license and collaboration agreement signed with Takeda in January 2024, the NDA submission initiates a 120-day period, after which Protagonist may choose to exercise an opt-out right during a subsequent 90-day window. Should Protagonist elect to opt out, it would be eligible to receive up to $400 million in opt-out payments, along with enhanced milestone opportunities and tiered royalties ranging from 14% to 29% on global net sales of rusfertide.
