This data is for laboratory research purposes only. Not for human or animal consumption.
What is Rusfertide?
Rusfertide (PTG-300, TAK-121), now FDA-approved and marketed as Mimrylo, is a synthetic hepcidin-mimetic peptide developed by Protagonist Therapeutics in collaboration with Takeda. It is approved as a first-in-class therapy for polycythemia vera (PV), a chronic myeloproliferative neoplasm characterized by excess red blood cell production (erythrocytosis). Unlike the other metabolic and neurological peptides in this database, rusfertide's target pathway is iron regulation and erythropoiesis rather than GLP-1/GIP signaling or GHRH/GABA pathways.
Mechanism of Action
Rusfertide mimics hepcidin, the liver-derived master regulator of systemic iron homeostasis. By binding ferroportin and blocking iron export from cells, it restricts the iron supply available for red blood cell production, lowering hematocrit without direct cytotoxic or myelosuppressive effects — a mechanistically distinct alternative to phlebotomy and cytoreductive drugs (hydroxyurea, interferon) in PV management.
Observed Clinical Results
- Phase 2 REVIVE trial (NEJM, Feb 2024; PMID 38381675; NCT04057040): In the randomized-withdrawal phase, 60% of rusfertide-treated patients maintained hematocrit control without phlebotomy versus 17% on placebo (P=.002); mean maximum hematocrit fell from 50.0% pre-treatment to 44.5% on rusfertide.
- Phase 3 VERIFY trial (NCT05210790, n=293): Rusfertide plus standard of care produced a 76.9% clinical response rate (freedom from phlebotomy eligibility, weeks 20-32) versus 32.9% for placebo plus standard of care — met primary endpoint and all four key secondary endpoints. Most common adverse reactions were injection site reactions and anemia.
- Long-term extension (REVIVE/THRIVE, ~4 years of data): Supports durable safety and efficacy, submitted as part of the NDA package.
Regulatory Status
FDA Approved — On August 28, 2026, the FDA approved Mimrylo (rusfertide) for adults with polycythemia vera, the first approved treatment that controls hematocrit by targeting the hepcidin pathway. The approval was granted to Takeda Pharmaceuticals America, Inc. following Priority Review, Breakthrough Therapy, Orphan Drug, and Fast Track designations. Not a compounding-pharmacy peptide — as an approved branded injectable specialty drug (Mimrylo), rusfertide is not 503A-eligible.