Rusfertide
InvestigationalA synthetic hepcidin mimetic peptide under FDA Priority Review for polycythemia vera. Phase 3 VERIFY trial demonstrated 77% hematocrit response rate. Developed by Protagonist Therapeutics (acquired by Takeda).
PTG-300 · Hepcidin Mimetic
12 human studies
- Preclinical
- 33%
- Human research
- 67%
Based on 18 cited sources
Numeric assessment unreviewed
A historical numeric score is recorded but has not passed a current, compound-specific assessment review. No numeric score is displayed.
This is a limitation of the numeric assessment, not a measured absence of benefit. It does not re-review the separately recorded catalogue classification or establish efficacy or safety.
How It Works (Simplified)
Rusfertide is a synthetic peptide that mimics hepcidin, the body’s master regulator of iron metabolism. By activating ferroportin degradation, it reduces iron absorption from the gut and iron release from storage cells, lowering the excess red blood cell production characteristic of polycythemia vera (PV). This mechanism directly addresses the iron-driven erythrocytosis in PV without the need for frequent phlebotomy.
Scientific Pathways
Hepcidin-Ferroportin Axis: Rusfertide binds to ferroportin (the sole cellular iron exporter), triggering its internalization and degradation. This reduces serum iron availability, limiting erythropoiesis and maintaining hematocrit within normal range.
Clinical Differentiation: Unlike JAK inhibitors (e.g., ruxolitinib) which target the inflammatory/proliferative component of myeloproliferative neoplasms, rusfertide specifically targets iron-driven erythrocytosis, offering a complementary mechanism.
Clinical Evidence
VERIFY Phase 3 Trial: The pivotal Phase 3 VERIFY trial (NCT05210790) is a 293-patient, placebo-controlled, add-on study in phlebotomy-requiring polycythemia vera. The sponsor reported topline results showing a 77% hematocrit response rate with rusfertide versus placebo. These Phase 3 results are topline (sponsor-reported) and have not yet been peer-reviewed or published; the trial remains ongoing through its long-term extension, and full results are not yet available.
REVIVE Phase 2 Data: The published evidence base is the Phase 2 REVIVE trial (NCT04057040; N Engl J Med 2024). During the 28-week dose-finding period, the mean number of phlebotomies fell from an estimated 8.7 per year before treatment to 0.6 per year on rusfertide, and mean maximum hematocrit was held below 45%. In the subsequent 12-week randomized-withdrawal period, a response occurred in 60% of patients on rusfertide versus 17% on placebo.
Safety Profile
The most common adverse events include injection site reactions (mild, transient), and iron deficiency (expected pharmacological effect requiring monitoring). No major cardiovascular or hepatic safety signals identified in trials to date. Long-term safety monitoring is ongoing through the VERIFY extension study.
Important Limitations
- Not yet FDA-approved (NDA under Priority Review, decision expected ~August 2026)
- Specific to polycythemia vera; not studied for other iron overload conditions
- Requires subcutaneous injection (not available orally)
- Long-term safety beyond clinical trial duration still being evaluated
- Iron parameters require monitoring during treatment
Use the source links in the research discussion above to inspect the referenced records.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength labels summarize the cited material for this entry and should be read alongside its population, model, and study limitations.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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