Peginesatide
A man-made peptide that switches on the erythropoietin receptor, approved for dialysis anaemia in 2012 and recalled within a year
Peginesatide is a synthetic erythropoiesis-stimulating agent: two identical 21-amino-acid peptides joined together and attached to a large polyethylene glycol chain. It shares no sequence with erythropoietin, yet it activates the same receptor and raises haemoglobin with one injection a month. FDA approved it as Omontys in March 2012 for anaemia in adults on dialysis. In February 2013 it was recalled after reports of severe, sometimes fatal allergic reactions shortly after a first dose, and it never returned. Anti-doping laboratories still test for it.
Last FDA label of a product discontinued in the US (not a current US recommendation): 0.04 mg/kg, Once monthly, Intravenous or subcutaneous Details ↓
Recommended Dosing
Last FDA label of a product discontinued in the US (not a current US recommendation)
From the last US prescribing information of a product discontinued in the US (see the regulatory status on this page). It records what that label said while the product was sold there; it is not a current US recommendation. Other doses studied, if any, are in the full dosing data below.
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Every erythropoiesis-stimulating agent (ESA) before peginesatide was a form of erythropoietin, the kidney hormone that tells bone marrow to make red cells, produced in cultured mammalian cells. Peginesatide was built differently. Chemists made a short peptide that binds and activates the erythropoietin receptor, joined two copies, and attached a branched 40 kDa polyethylene glycol chain to slow its removal. The result has no sequence in common with erythropoietin and is made by chemical synthesis. In laboratory cells it switched on the same signalling and genes as recombinant erythropoietin, and antibodies raised against one did not recognise the other.
That design promised two advantages: monthly dosing and freedom from the antibody problem that occasionally makes patients' marrow stop responding to erythropoietin altogether. In healthy volunteers a single intravenous dose raised reticulocytes and, at the highest dose, haemoglobin for more than a month. Phase 2 trials in kidney patients settled on dosing every four weeks, because dosing every two weeks more often pushed haemoglobin up too fast or too high, and worked out tables for switching patients from epoetin.
The phase 3 programme ran four large trials. In two trials in people on haemodialysis (EMERALD 1 and 2, 1,608 patients), monthly peginesatide held haemoglobin as well as epoetin given one to three times a week, and in the pooled cardiovascular safety analysis the hazard ratio was 1.06. In two trials in kidney patients not on dialysis (PEARL 1 and 2, 983 patients), it raised haemoglobin as well as darbepoetin, but deaths, unstable angina and arrhythmias were more frequent, with a hazard ratio of 1.32. FDA therefore approved Omontys in March 2012 only for adults on dialysis.
Commercial use began with a multi-use vial whose formulation differed from the single-use vials of the trials. Within months, reports of anaphylaxis and dangerous drops in blood pressure within minutes of a first injection accumulated, some of them fatal. The product was recalled in February 2013. A Medicare claims study later found that on the day of a first peginesatide dose, death or hospital care for cardiovascular events was 2.7 times as likely as after an epoetin dose. An analysis of FDA particle images found that the lots linked to severe reactions could be told apart from the others, and a 2017 commentary tied the reactions to the multi-use vial formulation and its phenol; whether the molecule itself was blameless has never been settled in people.
Peginesatide is not sold anywhere now. Its EU application was withdrawn in 2013, and US records list every strength as discontinued. It remains named on WADA's Prohibited List as an erythropoietin-receptor agonist, and doping scientists have warned that interest could return because the reactions were tied to one formulation. The doses below are from the last US label and the trials; they explain the research, not a dose anyone can obtain.
Mechanism of Action
Peginesatide is an erythropoietin-receptor agonist built from synthetic peptides rather than from the erythropoietin protein.
Receptor activation
Binds and activates the erythropoietin receptor, triggering the same phosphorylation and gene programme as erythropoietin (PMIDs 16982323, 22406924).
More red cells
Raises reticulocytes and then haemoglobin, at a rate that depends on dose (PMID 16720830).
Immunologically distinct
Antibodies to erythropoietin do not recognise it, so it corrected antibody-driven anaemia in rats (PMID 17662888).
Published Research
Studies of peginesatide (earlier called Hematide) read from their PubMed abstracts: the phase 3 EMERALD and PEARL trials, phase 1 and 2 dose-finding and conversion studies, pharmacokinetic and heart-rhythm studies, the post-recall safety and formulation analyses, two reviews, and the cell and animal work behind it.
EMERALD 1 and 2: dialysis patients
1,608 haemodialysis patients were randomised to monthly peginesatide or continued epoetin one to three times a week for at least 52 weeks. Peginesatide was noninferior for holding haemoglobin (differences of -0.15 and 0.10 g/dL), and across all four phase 3 trials the composite cardiovascular safety hazard ratio was 1.06.
PEARL 1 and 2: not on dialysis
983 kidney patients not on dialysis received monthly peginesatide starting at 0.025 or 0.04 mg/kg, or darbepoetin every two weeks. Peginesatide raised and held haemoglobin as well as darbepoetin, but the cardiovascular safety hazard ratio was 1.32, with more deaths, unstable angina and arrhythmia.
First trial in healthy men
28 healthy men received single intravenous doses of 0.025, 0.05 or 0.1 mg/kg or placebo. Reticulocytes rose with dose, and 0.1 mg/kg raised haemoglobin by about 1.4 g/dL against 0.4 on placebo, an effect that lasted over a month; safety resembled placebo.
Dose-finding without dialysis
139 kidney patients not on dialysis were assigned to cohorts differing in dose, route and frequency. 96% had a haemoglobin response; dosing every two weeks caused more rapid rises and excursions over 13 g/dL than every four weeks, and final monthly doses ran from 0.019 to 0.043 mg/kg.
Switching from epoetin on haemodialysis
164 haemodialysis patients were switched from epoetin to intravenous peginesatide every four weeks under different conversion rules. Tiered conversion tables gave steadier doses than a single ratio, and a one-week gap without any ESA avoided an early overshoot in haemoglobin; the results shaped the phase 3 dosing.
Switching from darbepoetin
In 101 patients converted from darbepoetin to monthly peginesatide for 24 weeks, haemoglobin fell slightly in those on haemodialysis (-0.42 g/dL) and rose slightly in those not on dialysis (+0.49 g/dL); about 70% to 80% stayed within 1 g/dL of baseline.
Peritoneal dialysis
59 peritoneal dialysis patients switched from epoetin to monthly peginesatide (median starting dose 0.047 mg/kg) kept a mean haemoglobin of 11.3 g/dL over 25 weeks; 10% needed transfusion and peritonitis was the most common adverse event.
Population pharmacokinetics
Using 2,665 plasma samples from 672 kidney patients, the authors described peginesatide with a two-compartment model with saturable elimination and linked its levels to haemoglobin; no patient factor changed exposure enough to matter clinically.
No effect on the QT interval
In a three-way crossover in healthy adults, a single 0.1 mg/kg intravenous dose did not prolong the corrected QT interval, with an upper confidence bound of 2.2 milliseconds, and did not change heart rate or other ECG intervals.
Medicare claims after the launch
Comparing 15,633 dialysis patients given peginesatide with 31,266 matched patients given epoetin, death or hospital care for cardiovascular events on the day of the first dose occurred in 0.12% against 0.04% (hazard ratio 2.7), with smaller excesses over the next two days.
Particles in the implicated lots
FDA flow-microscopy images of particles from peginesatide lots tied to severe reactions, including seven deaths, could be told apart from images of lots without such reactions, using new methods for comparing particle shapes.
An unfulfilled promise
This review describes peginesatide's advantages in immunogenicity, dosing schedule and cost, explains why its approval was limited to dialysis patients, and recounts the unexplained serious reactions that led to its quick withdrawal, as a lesson in how rare harms escape trials.
The case for it, at approval
Written soon after US approval, this review judged the data to favour peginesatide over epoetin in dialysis patients and called for more safety work in patients not on dialysis and for comparisons with longer-acting epoetin.
A warning to anti-doping labs
This commentary notes that peginesatide was recalled for anaphylactoid reactions with a fatality rate of about 0.02%, that later work tied the reactions to the multi-use vial formulation and its phenol rather than the drug substance, and that athletes might therefore try it; it urges better detection methods.
The same signals as erythropoietin
In an erythropoietin-dependent human cell line, peginesatide and recombinant erythropoietin caused tyrosine phosphorylation of essentially the same proteins and changed the expression of a similar set of genes.
Preclinical profile
The compound bound and activated the erythropoietin receptor, drove growth of human red-cell progenitors in culture, persisted in the blood of rats and monkeys, raised haemoglobin in a dose-dependent way, corrected anaemia in rats with kidney insufficiency and induced no antibodies on repeat dosing in rats.
Anaemia caused by anti-erythropoietin antibodies
Antibodies against erythropoietin did not bind peginesatide and vice versa, and in rats made anaemic by antibodies to erythropoietin, peginesatide corrected the anaemia.
Nine months in monkeys
Monkeys given 0.2 to 20 mg/kg intravenously every three weeks for nine months developed too many red cells, rising with dose, and the tissue findings were attributed to that exaggerated effect in animals that were not anaemic.
Where it goes in monkeys
After one intravenous dose, peginesatide was cleared slowly with a small volume of distribution and a long half-life, concentrated in bone marrow and other blood-forming sites for at least three weeks, was not metabolised, and left mainly in urine.
Where it goes in rats
In rats, unchanged peginesatide made up over 90% of circulating radioactivity, collected in bone marrow and blood-forming tissues, sometimes lost one arm of its branched PEG, and was eliminated mainly through the kidneys.
Dosing Data
The first rows are the last US label for Omontys, revised in December 2012. Every Omontys product was recalled in February 2013 and is listed as discontinued, so these figures explain the trials; no one can obtain the product. The last row is a starting dose from the PEARL trials in patients not on dialysis, a use the label excluded.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Peginesatide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: we hold no copy of the preparation section of the label behind Peginesatide's dose. Its label, named in Recommended Dosing above, is the source; the reconstitution calculator does the arithmetic for any vial.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Peginesatide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Peginesatide stays intact once mixed.
How it is taken
As the approved label gives it: Intravenous or subcutaneous (Once monthly; Last US label (Omontys, discontinued): patients on dialysis not already on an ESA); Same route as before (Once monthly; Last US label (Omontys, discontinued): switching from epoetin alfa or darbepoetin alfa).
Source: Last FDA label of a product discontinued in the US (not a current US recommendation): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 48 hours in dialysis patients (intravenous); 25 hours intravenous and 53 hours subcutaneous in healthy subjects. After about five half-lives almost none is left.
How long the doses were given: Last US label (Omontys, discontinued): patients on dialysis not already on an ESA: Start when haemoglobin is below 10 g/dL; adjust no more than every 4 weeks; Last US label (Omontys, discontinued): switching from epoetin alfa or darbepoetin alfa: First dose one week after the last epoetin dose, or at the next darbepoetin dose; Last US label (Omontys, discontinued): dose adjustment: Reduce or pause as haemoglobin nears 11 g/dL.
When effects appear: unknown; no source on this page gives a time to effect for Peginesatide. Results reported in the studies are under Published Research.
Source: half-life: Omontys (peginesatide) injection US prescribing information, revised December 2012, the last version on Drugs@FDA (NDA 202799), Clinical Pharmacology; Last FDA label of a product discontinued in the US (not a current US recommendation), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Severe allergic reactions within minutes of a first dose after launch, some fatal, leading to the February 2013 recall (PMIDs 24905967, 27279382); More deaths, unstable angina and arrhythmia than darbepoetin in patients not on dialysis (PMID 23343062); Haemoglobin rising too fast or too high, more often with dosing every two weeks (PMID 21940838); Antibodies against peginesatide in a small share of patients (Omontys label); Peritonitis and other events typical of dialysis populations in the trials (PMID 24584613). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Peginesatide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials and post-marketing studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Peginesatide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Peginesatide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (US: Omontys, NDA 202799, approved March 27, 2012 for anaemia of chronic kidney disease in adults on dialysis). Sport: Prohibited at all times (S2.1.1).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the trials and post-marketing studies above.
Contraindications & Cautions
From the last US label (revised December 2012), which carried the boxed warning shared by all ESAs.
Legal Status
Peginesatide was briefly approved in the US and has been off the market everywhere since 2013.
Frequently Asked Questions
?How is peginesatide different from EPO?
It is not a form of erythropoietin. It is a synthetic peptide dimer with a PEG chain that activates the same receptor. It shares no sequence with EPO and is made chemically rather than in cell culture.
?Why was it recalled?
Soon after launch, patients had severe allergic reactions, including some deaths, usually within minutes of their first dose. The product was recalled in February 2013. The reactions were later linked to the multi-use vial formulation, but this was never proven in patients.
?Did it work?
Yes. In dialysis patients, monthly injections held haemoglobin as well as epoetin given up to three times a week. In patients not on dialysis it worked but carried more cardiovascular events than darbepoetin.
?Can it be bought now?
No approved product exists anywhere. Any material sold under this name comes from unregulated sources, with unknown content and the same unexplained allergy risk.
?Is it banned in sport?
Yes. WADA names peginesatide on its Prohibited List among erythropoietin-receptor agonists, and doping laboratories have methods to detect it.
?Why does it come up in doping discussions?
Because it raises red cells for weeks after one injection and was tied to a specific formulation's reactions, a 2017 commentary warned that athletes might try it again.
References
- [other] US FDA, Drugs@FDA (openFDA): OMONTYS and OMONTYS PRESERVATIVE FREE, NDA 202799, original approval March 27, 2012; marketing status discontinued. Read October 28, 2026.
- [other] European Medicines Agency, medicines list (JSON report, downloaded October 28, 2026): Omontys (peginesatide): marketing application withdrawn, withdrawal date June 28, 2013; for symptomatic anaemia associated with chronic kidney disease.
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT00597584 (phase 3, maintenance treatment of anaemia in chronic kidney disease, completed); NCT00434330 (phase 2, haemodialysis, completed).
- [other] Omontys (peginesatide) injection, US prescribing information, revised December 2012 (NDA 202799, supplement 1; Affymax and Takeda). Drugs@FDA label archive, read October 29, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202799s001lbl.pdf
- [clinical-trial] Fishbane S, et al. "Peginesatide in patients with anemia undergoing hemodialysis." N Engl J Med, 2013;368(4):307-19. PMID: 23343061.
- [clinical-trial] Macdougall IC, et al. "Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis." N Engl J Med, 2013;368(4):320-32. PMID: 23343062.
- [clinical-trial] Stead RB, et al. "Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers." Blood, 2006;108(6):1830-4. PMID: 16720830.
- [clinical-trial] Macdougall IC, et al. "Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients." Clin J Am Soc Nephrol, 2011;6(11):2579-86. PMID: 21940838.
- [clinical-trial] Besarab A, et al. "An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients." BMC Nephrol, 2012;13:95. PMID: 22935486.
- [clinical-trial] Fishbane S, et al. "Peginesatide for maintenance treatment of anemia in hemodialysis and nondialysis patients previously treated with darbepoetin alfa." Clin J Am Soc Nephrol, 2013;8(4):538-45. PMID: 23243269.
- [clinical-trial] Zabaneh R, et al. "Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis." Perit Dial Int, 2015;35(4):481-9. PMID: 24584613.
- [pubmed] Naik H, et al. "A Population Pharmacokinetic and Pharmacodynamic Analysis of Peginesatide in Patients with Chronic Kidney Disease on Dialysis." PLoS One, 2013;8(6):e66422. PMID: 23840463.
- [clinical-trial] Czerniak R, et al. "Effects of Peginesatide Injection on QTc Interval in Healthy Adults." Clin Pharmacol Drug Dev, 2014;3(6):449-455. PMID: 26161294.
- [pubmed] Weinhandl ED, et al. "Relative safety of peginesatide and epoetin alfa." Pharmacoepidemiol Drug Saf, 2014;23(10):1003-11. PMID: 24905967.
- [pubmed] Daniels AL, et al. "Flow Microscopy Imaging Is Sensitive to Characteristics of Subvisible Particles in Peginesatide Formulations Associated With Severe Adverse Reactions." J Pharm Sci, 2018;107(5):1313-1321. PMID: 29409840.
- [review] Hermanson T, et al. "Peginesatide for the treatment of anemia due to chronic kidney disease - an unfulfilled promise." Expert Opin Drug Saf, 2016;15(10):1421-6. PMID: 27551882.
- [review] Schmid H, et al. "Peginesatide for the treatment of renal disease-induced anemia." Expert Opin Pharmacother, 2013;14(7):937-48. PMID: 23506424.
- [review] Jelkmann W, et al. "Watch out for a revival of peginesatide in sports." Drug Test Anal, 2017;9(2):157-160. PMID: 27279382.
- [pubmed] Green JM, et al. "Peginesatide and erythropoietin stimulate similar erythropoietin receptor-mediated signal transduction and gene induction events." Exp Hematol, 2012;40(7):575-87. PMID: 22406924.
- [pubmed] Fan Q, et al. "Preclinical evaluation of Hematide, a novel erythropoiesis stimulating agent, for the treatment of anemia." Exp Hematol, 2006;34(10):1303-11. PMID: 16982323.
- [pubmed] Woodburn KW, et al. "Hematide is immunologically distinct from erythropoietin and corrects anemia induced by antierythropoietin antibodies in a rat pure red cell aplasia model." Exp Hematol, 2007;35(8):1201-8. PMID: 17662888.
- [pubmed] Woodburn KW, et al. "Chronic preclinical safety evaluation of Hematide, a pegylated peptidic erythropoiesis stimulating agent in monkeys." Haematologica, 2008;93(9):1376-9. PMID: 18519511.
- [pubmed] Woodburn KW, et al. "Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration." Drug Metab Dispos, 2013;41(4):774-84. PMID: 23318685.
- [pubmed] Woodburn KW, et al. "Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats." Xenobiotica, 2012;42(7):660-70. PMID: 22188389.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Doses, half-life and the boxed warning come from the December 2012 Omontys label on Drugs@FDA; status from Drugs@FDA (openFDA), the EMA medicines list and ClinicalTrials.gov, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.