OSAKA, JAPAN & CAMBRIDGE, MASS. & NEWARK, CALIF. -- Takeda (TSE:4502/NYSE:TAK) and Protagonist Therapeutics (Nasdaq: PTGX) (“Protagonist”) announced the submission of 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). Rusfertide is an investigational first-in-class subcutaneously administered hepcidin mimetic peptide designed to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV.

“This is an important milestone toward our goal of addressing critical gaps that patients living with polycythemia vera face today,” said Teresa Bitetti, President, Global Oncology Business Unit, Takeda. “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.”

This NDA submission follows the positive 32-week primary analysis and 52-week results from the Phase 3 global randomized, placebo-controlled VERIFY study (NCT05210790), in which rusfertide met the primary endpoint and all four key secondary endpoints, as well as the Phase 2 REVIVE study (NCT04057040). In the VERIFY study, patients receiving rusfertide plus standard of care therapy demonstrated a substantially higher response rate compared to placebo plus standard of care, including durable hematocrit control, a reduction in phlebotomy requirements and improvement in pre-specified patient reported outcome (PRO) endpoints.

Rusfertide has received Breakthrough Therapy Designation, a regulatory milestone recognizing the potential of rusfertide to offer a substantial improvement over available therapies, as well as Orphan Drug Designation and Fast Track Designation from the U.S. FDA.

“Rusfertide has the potential to redefine the treatment paradigm for PV by offering patients a novel, first-in-class erythrocytosis-specific therapy that significantly reduces or eliminates the need for frequent phlebotomy,” said Dinesh V. Patel, Ph.D., Protagonist President and CEO. “Submitting this NDA marks a major inflection point in the decade long journey that started with a hepcidin mimetic program at Protagonist. Rusfertide has practice-changing potential that could become standard of care for patients with PV who currently rely on burdensome and often ineffective therapies.”

Under the terms of its January 2024 worldwide license and collaboration agreement with Takeda, the submission of the NDA triggers the start of a 120-day period, after which Protagonist can decide to exercise its opt-out right during a subsequent 90-day period. If Protagonist chooses to exercise this opt-out right, it would be eligible to receive up to $400 million in opt-out payments as well as enhanced milestone payments and 14-29% tiered royalty rates on worldwide net sales of rusfertide.