CAMBRIDGE, Mass.– Takeda and Protagonist Therapeutics have submitted a New Drug Application to the U.S. Food and Drug Administration seeking approval of rusfertide for the treatment of adults with polycythemia vera, a rare blood cancer characterized by excessive red blood cell production.
Rusfertide is an investigational, first-in-class hepcidin mimetic peptide administered subcutaneously and designed to regulate iron homeostasis and control erythrocytosis, helping patients maintain appropriate hematocrit levels.
The NDA is supported by 52-week data from the Phase 3 global, randomized, placebo-controlled VERIFY study, which met its primary endpoint and all four key secondary endpoints. Results showed that rusfertide provided durable and sustained hematocrit control, reduced the need for phlebotomies, and improved pre-specified patient-reported outcome measures when added to standard-of-care therapy. The application also includes data from the Phase 2 REVIVE study.
“This is an important milestone toward our goal of addressing critical gaps that patients living with polycythemia vera face today,” said Teresa Bitetti, president of Takeda’s Global Oncology Business Unit. “The comprehensive VERIFY study data underscore rusfertide’s strong clinical profile and potential to provide sustained hematocrit control while reducing phlebotomy and symptom burden. Our collaboration with Protagonist exemplifies how partnerships can advance innovative science with a focus on making a meaningful difference for patients.”
In the VERIFY study, patients treated with rusfertide plus standard of care demonstrated substantially higher response rates compared with those receiving placebo plus standard of care. Benefits included durable hematocrit control, fewer required phlebotomies, and improvements across multiple patient-reported outcome endpoints.
Rusfertide has received Breakthrough Therapy Designation from the FDA, as well as Orphan Drug and Fast Track designations, reflecting its potential to offer a significant improvement over existing therapies.
“Rusfertide has the potential to redefine the treatment paradigm for polycythemia vera by offering patients a novel, erythrocytosis-specific therapy that significantly reduces or eliminates the need for frequent phlebotomy,” said Dinesh V. Patel, Ph.D., president and chief executive officer of Protagonist Therapeutics. “Submitting this NDA marks a major inflection point in a decade-long journey that began with a hepcidin mimetic program at Protagonist.”
Under the terms of the companies’ worldwide license and collaboration agreement signed in January 2024, the NDA submission initiates a 120-day period after which Protagonist may elect 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 global net sales of rusfertide.
