Rusfertide
InvestigationalAlso known as: PTG-300, Hepcidin Mimetic
A 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).
Research Statistics
Phase 3 complete with strong efficacy. NDA under Priority Review.
Research Dossier
Overview
What is Rusfertide and what does the research say?
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 VERIFY trial (NCT04057040) demonstrated a 77% hematocrit response rate with rusfertide versus phlebotomy-dependent standard of care. Patients achieved sustained hematocrit control below 45% with significant reduction in phlebotomy requirements.
Phase 2 Data: Earlier Phase 2 trials showed durable hematocrit control over 28 weeks, with 92% of patients eliminating phlebotomy dependence. Data presented at ASH (American Society of Hematology) annual meetings.
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
References
Full reference list available on request. All citations link to PubMed for verification.
Methodology Note
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
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.
Get Research Alerts
New dossiers and major study summaries delivered to your inbox. Evidence-graded, citation-backed research you can trust.
No spam. Unsubscribe anytime.
Related Peptides
225Ac-DOTA-LM3
Actinium-225-DOTA-LM3, 225Ac-DOTA-JR11, Alpha-PRRT +1 more
An alpha-emitting radiolabeled somatostatin receptor antagonist for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors. Unlike conventional beta-emitting Lu-177 therapies and SSTR agonists, 225Ac-DOTA-LM3 combines the higher cell-killing power of alpha particles with antagonist binding for enhanced tumor targeting. Clinical stage investigational therapy showing promise in Lu-177-refractory patients.
Bronchogen
AEDL, Ala-Glu-Asp-Leu, Bronchial tetrapeptide +1 more
A synthetic tetrapeptide (Ala-Glu-Asp-Leu) developed by Russian scientist Vladimir Khavinson for bronchial and respiratory tissue support. Claimed to modulate bronchial epithelium gene expression and provide respiratory protective effects. No Western clinical validation; all evidence from Russian bioregulator research.
BT5528
Bicycle Toxin Conjugate 5528, EphA2-BTC
A first-in-class Bicycle Toxin Conjugate (BTC) targeting EphA2-expressing tumors, developed by Bicycle Therapeutics. Combines a constrained bicyclic peptide targeting moiety with the cytotoxic payload MMAE. Phase 1/2 dose expansion ongoing with 67% ORR reported in EphA2-positive urothelial cancer patients.
Cardiogen
AED, Ala-Glu-Asp, Cardiac tripeptide
A synthetic tripeptide (Ala-Glu-Asp) developed by Russian scientist Vladimir Khavinson for cardiac tissue support. Claimed to target cardiomyocyte gene expression and provide cardioprotective effects. No Western clinical validation exists; evidence limited to Russian preclinical and observational studies.
Chelohart
Heart cytamin, Cardiac peptide supplement, A-7 heart peptides
A cytamin-class peptide supplement derived from cardiac (heart) tissue, part of the Khavinson bioregulator framework. Marketed as an oral supplement for cardiac health support. Contains peptide complexes rather than defined sequences. Very limited clinical validation, primarily Russian-language literature.
Chonluten
EDG-GI, Glu-Asp-Gly (GI), GI tract tripeptide +1 more
A synthetic tripeptide (Glu-Asp-Gly) developed by Vladimir Khavinson for gastrointestinal tissue support. Shares the same amino acid sequence as Kristagen but is marketed for digestive system rather than immune function. Limited to Russian studies with no Western validation or clinical trials.