Takeda and Protagonist Submit NDA to FDA for Rusfertide in Polycythemia Vera

Takeda and Protagonist Therapeutics have announced the submission of a New Drug Application to the U.S. Food and Drug Administration for Rusfertide as a treatment for adults with Polycythemia vera. The filing represents a key regulatory milestone for the investigational therapy, which is being positioned as a potential new option to help patients achieve sustained hematocrit control while reducing dependence on phlebotomy.

Rusfertide is a first-in-class hepcidin mimetic designed to address the underlying iron dysregulation that drives excessive red blood cell production in PV. By restoring physiologic iron balance, the therapy aims to control erythrocytosis without the cumulative burden associated with repeated blood removal or long-term cytoreductive therapy. Rusfertide is administered as a once-weekly subcutaneous injection.

The NDA is supported by a comprehensive clinical data package anchored by the global Phase 3 VERIFY trial (NCT05210790) which evaluated Rusfertide added to standard of care in adults with Polycythemia vera. At 52 weeks, 61.9% of patients receiving continuous Rusfertide achieved sustained hematocrit control below 45% without phlebotomy, and 84.1% of responders-maintained control during the key weeks 20 to 32 assessment period, demonstrating durable efficacy. Rusfertide treatment was also associated with a significant reduction in phlebotomy requirements and clinically meaningful improvements in patient-reported outcomes related to PV symptom burden. These results were supported by a safety profile consistent with earlier studies and reinforced by data from prior clinical trials.

Pharmacally has previously reported in detail on the VERIFY Phase 3 results, including trial design, key endpoints, efficacy outcomes, safety profile, and patient-reported benefits presented at ASH 2025. Those data now form the core clinical foundation of the regulatory submission and provide important context for understanding the strength of the NDA.

Takeda and Protagonist leadership described the NDA submission as a defining step toward improving care for patients with polycythemia vera.

Teresa Bitetti, President of Takeda’s Global Oncology Business Unit, said the filing represents an important milestone in addressing persistent gaps in PV treatment. She emphasized that data from the VERIFY Phase 3 study highlight Rusfertide strong clinical profile, including sustained hematocrit control with reduced phlebotomy and symptom burden, and noted that the collaboration with Protagonist reflects a shared commitment to delivering meaningful benefits for patients.

Dinesh V. Patel, President and CEO of Protagonist Therapeutics, described the NDA submission as a major inflection point in the company’s decade-long hepcidin mimetic program. He stated that Rusfertide has the potential to redefine the PV treatment paradigm as a first-in-class, erythrocytosis-specific therapy that could significantly reduce or eliminate reliance on frequent phlebotomy and become a new standard of care for patients who currently depend on burdensome and often suboptimal therapies.

The NDA submission is supported not only by the pivotal Phase 3 VERIFY trial but also by a broader clinical development program evaluating Rusfertide across different PV treatment settings. This includes the completed Phase 2 REVIVE study (NCT04057040), which demonstrated sustained hematocrit control and meaningful reductions in phlebotomy when Rusfertide was added to standard therapy, helping inform dose selection and long-term use strategies.

In parallel, the ongoing THRIVE program (NCT06033586) is evaluating Rusfertide in patients with PV receiving cytoreductive therapies, with the aim of further characterizing its role across the treatment continuum and generating additional long-term safety and durability data. Together, these studies form a comprehensive evidence base underpinning the NDA and supporting Rusfertide potential integration into routine PV management pending regulatory review.