Takeda and Protagonist Therapeutics have submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of rusfertide for the treatment of adults with polycythemia vera (PV), a rare and chronic blood cancer characterized by excessive red blood cell production. The filing marks a significant regulatory milestone for the companies and could pave the way for a new treatment option aimed at addressing persistent unmet needs in PV care.
Rusfertide is an investigational, first-in-class hepcidin mimetic peptide administered subcutaneously. It is designed to regulate iron homeostasis and red blood cell production, thereby helping control hematocrit levels in patients with PV. Current standard treatments often rely on repeated phlebotomy and cytoreductive therapies, which can be burdensome for patients and may not provide sustained disease control. Rusfertide’s mechanism targets the underlying dysregulation of iron metabolism that drives erythrocytosis, offering a novel approach distinct from existing therapies.
The NDA submission is supported by data from the Phase 3 global, randomized, placebo-controlled VERIFY study as well as the earlier Phase 2 REVIVE study. In the VERIFY trial, rusfertide met its primary endpoint and all four key secondary endpoints at the 32-week primary analysis, with benefits maintained through 52 weeks. Patients treated with rusfertide in combination with standard of care demonstrated significantly higher response rates compared with those receiving placebo plus standard therapy. Key outcomes included durable control of hematocrit levels, a marked reduction in the need for phlebotomy, and improvements across pre-specified patient-reported outcome measures, highlighting both clinical and quality-of-life benefits.
Takeda emphasized the potential impact of these results for patients living with PV. According to Teresa Bitetti, President of Takeda’s Global Oncology Business Unit, the VERIFY data underscore rusfertide’s strong clinical profile and its ability to reduce treatment burden while delivering sustained disease control. She noted that the collaboration with Protagonist reflects a shared commitment to advancing innovative science with the goal of making a meaningful difference for patients.
Rusfertide has already received several important regulatory designations from the FDA, including Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation. These recognitions highlight the therapy’s potential to offer substantial improvement over available treatments and are intended to facilitate a more expedited development and review process.
Protagonist Therapeutics also highlighted the significance of the NDA filing. President and CEO Dinesh V. Patel described rusfertide as a potential paradigm-shifting therapy that could significantly reduce or eliminate the need for frequent phlebotomy, which remains a cornerstone but often challenging aspect of PV management. He characterized the submission as a major inflection point in a decade-long development journey for the company’s hepcidin mimetic program.
The NDA submission also has strategic and financial implications under the companies’ January 2024 worldwide license and collaboration agreement. The filing triggers a 120-day period after which Protagonist may choose to exercise an opt-out right during a subsequent 90-day window. If exercised, Protagonist would be eligible to receive up to $400 million in opt-out payments, along with enhanced milestone payments and tiered royalties ranging from 14% to 29% on worldwide net sales of rusfertide.