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Peginesatide

Also known as: Omontys, Hematide, AF37702, PEGylated Erythropoiesis-Stimulating Peptide

Peginesatide (Omontys) was a PEGylated synthetic erythropoiesis-stimulating peptide designed as a once-monthly alternative to erythropoietin (EPO) for treating anemia in chronic kidney disease patients on dialysis. Unlike traditional ESAs, it was not derived from EPO and had no sequence homology to erythropoietin, representing a novel approach to erythropoiesis stimulation. FDA-approved in March 2012, it was voluntarily withdrawn from the market in February 2013 after reports of serious hypersensitivity reactions, including fatal anaphylaxis.

3 cited references·4 researched benefits

Quick Answer

Peginesatide (Omontys) was a once-monthly PEGylated synthetic peptide that stimulated red blood cell production by activating the erythropoietin receptor without any structural similarity to EPO. FDA-approved in 2012 for anemia in dialysis-dependent chronic kidney disease, it was withdrawn in 2013 after serious and fatal anaphylactic reactions during post-marketing use. Its story illustrates both the promise and risks of novel peptide therapeutics and the importance of post-marketing pharmacovigilance.

Key Facts

Mechanism
Peginesatide consists of two identical 21-amino acid peptide chains linked to a PEG (polyethylene glycol) moiety. Despite having no sequence homology to erythropoietin, the peptide dimers bind to and activate the erythropoietin receptor (EpoR) homodimer on erythroid progenitor cells in bone marrow. This activates the JAK2-STAT5 signaling cascade, promoting proliferation, differentiation, and survival of erythroid precursors, ultimately increasing red blood cell production and hemoglobin levels. The PEG component extends half-life sufficiently for once-monthly dosing. Importantly, because peginesatide has no structural similarity to EPO, it was not affected by anti-EPO antibodies in patients with pure red cell aplasia.
Research Status
approved
Half-Life
~25–40 hours (supports once-monthly dosing due to PEGylation)
Molecular Formula
C₂₉₈H₄₈₈N₆₈O₁₂₅S₄·PEG
Primary Use
Other
Table of Contents

Benefits

  • Once-monthly dosing for anemia management — improved convenience over 1–3× weekly EPO injectionsstrong
  • Non-inferior to epoetin for maintaining hemoglobin 10–12 g/dL in dialysis patients (EMERALD trials)strong
  • No cross-reactivity with anti-EPO antibodies — potential treatment for pure red cell aplasia caused by anti-EPO antibodiesmoderate
  • Novel pharmacology — demonstrated that synthetic peptides can replace complex recombinant proteins for receptor activationmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous or subcutaneous injection0.04 mg/kg initial, adjusted to maintain Hgb 10–11 g/dLOnce monthlyWITHDRAWN FROM MARKET. Historical dosing information provided for reference only. Dose was individualized based on hemoglobin response, with adjustments every 4 weeks. Administered as IV bolus in dialysis patients or subcutaneously in non-dialysis patients.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Serious hypersensitivity and anaphylaxis — the primary reason for market withdrawal, with fatal cases reportedserious
  • Hypertension — class effect of erythropoiesis-stimulating agents, occurring in 10–15% of patientscommon
  • Diarrhea, nausea, and vomitingcommon
  • Arteriovenous fistula thrombosis in dialysis patientscommon
  • Increased cardiovascular risk (stroke, MI, thromboembolic events) — class effect when targeting hemoglobin >11 g/dLserious
  • Seizures — associated with rapid hemoglobin rise, a risk shared with all ESAsserious

Frequently Asked Questions

Why was peginesatide (Omontys) withdrawn from the market?
Peginesatide was voluntarily recalled by Affymax and Takeda in February 2013, less than one year after FDA approval, following 19 reports of serious hypersensitivity reactions (including 3 deaths) within 30 minutes of the first intravenous dose. The anaphylactic reactions were likely mediated by anti-PEG antibodies or complement activation by the large PEG moiety. The FDA issued a safety alert, and the manufacturers voluntarily withdrew the product from all markets globally. Approximately 25,000 patients had received the drug before withdrawal.
How was peginesatide different from EPO?
Peginesatide was a completely synthetic peptide with zero sequence homology to human erythropoietin. Traditional ESAs (epoetin alfa, darbepoetin) are recombinant versions of the naturally occurring EPO glycoprotein. Despite being structurally unrelated, peginesatide activated the same EPO receptor to stimulate red blood cell production. This made it a potential treatment for the rare condition of pure red cell aplasia caused by anti-EPO antibodies, since those antibodies would not neutralize peginesatide.
Could peginesatide have been used for sports doping?
Theoretically, yes. Because peginesatide stimulates erythropoiesis like EPO, it could increase red blood cell mass and oxygen-carrying capacity. Moreover, since it has no structural similarity to EPO, traditional anti-doping tests for recombinant EPO would not detect it. WADA (World Anti-Doping Agency) classified peginesatide as a prohibited substance. Specific detection methods using mass spectrometry were developed to identify it in athlete samples. Its market withdrawal largely eliminated this concern.
What lessons did the peginesatide withdrawal teach the pharmaceutical industry?
The peginesatide case highlighted several important lessons: (1) PEGylation, while extending drug half-life, can trigger complement activation and anti-PEG immune responses, especially with large PEG moieties; (2) post-marketing pharmacovigilance is critical, as serious hypersensitivity was not detected in clinical trials of approximately 2,600 patients; (3) first-dose monitoring is essential for IV-administered biologics; and (4) the importance of risk-benefit assessment — alternative ESAs with decades of safety data were available.

References

  1. 1
    Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis (PEARL trials)(2013)PubMed ↗
  2. 2
    Peginesatide for anemia in patients with chronic kidney disease on dialysis (EMERALD trials)(2013)PubMed ↗
  3. 3
    Pharmacovigilance and the withdrawal of peginesatide: lessons learned(2013)PubMed ↗

Latest Research

Last updated: 2026-02-19