LTP·01learntopeptide
OtherEvidence B4 cited

Peginesatide

aka Omontys · Affymax EPO mimetic · AF37702

Peginesatide is a synthetic PEGylated peptide-based erythropoiesis-stimulating agent (ESA) that activates the erythropoietin (EPO) receptor to stimulate red blood cell production. Marketed briefly as Omontys, it was designed as an alternative to recombinant EPO products for treating anemia in chronic kidney disease. Unlike traditional ESAs, peginesatide is a synthetic dimeric peptide with no structural homology to erythropoietin, developed to avoid anti-EPO antibody-mediated pure red cell aplasia. It received FDA approval in March 2012 but was voluntarily withdrawn in February 2013 following reports of serious hypersensitivity reactions including fatal anaphylaxis. Research interest continues in modified formulations and the synthetic peptide EPO agonist concept remains scientifically valid.

Withdrawn from market
Yes. On 23 February 2013 - approximately 11 months after approval - Affymax and Takeda announced a nationwide voluntary recall of ALL lots of OMONTYS, following post-marketing reports of serious hypersensitivity reactions including anaphylaxis, which were life-threatening and in some cases fatal. Reactions occurred typically within 30 minutes of the first intravenous dose in dialysis patients. The product never returned to market, and FDA formally withdrew approval of NDA 202799 on 13 February 2019 at Takeda's own request, with the sponsor waiving its opportunity for a hearing.
Molecular wt
Approximately 45,000 total (dimeric peptide core approximately 4,900; PEG chain approximately 40,000)g/mol
Formula
C2031H3950N62O958S6 (free base, as printed in the FDA label; the O and PEG content reflect the ~40 kDa PEG moiety)
CAS
913976-27-9 (NCATS Inxight also lists 1350810-60-4 for this substance)
Half-life
1 days
established
Tmax
2 days
Route
Subcutaneous injection

Sequence

Read this before quoting the sequence
A synthetic PEGylated DIMERIC peptide. The FDA label describes it as 'comprised of two identical, 21-amino acid chains covalently bonded to a linker derived from iminodiacetic acid and beta-alanine', with the two chains attached to a single lysine-branched bis-(methoxypolyethylene glycol) chain of approximately 40,000 Da. The chain contains the non-proteinogenic residue 1-naphthylalanine (1Nal) and an intrachain disulfide, so a standard one-letter string is not applicable. CAVEAT: only 19 named residues could be extracted from the label text; the label states 21 per chain, with the remaining residues (including a sarcosine and the branching lysine) shown only in the structural diagram, which could not be read as text. Treat the residue list as partial. Peginesatide has NO amino acid sequence homology to erythropoietin.
Source ↗

Mechanism of action

Peginesatide consists of two identical 21-amino-acid synthetic peptide chains linked by a PEG moiety. Despite having no sequence homology to endogenous erythropoietin, the dimeric peptide binds to and activates the EPO receptor (EPOR) on erythroid progenitor cells in bone marrow. This triggers the JAK2-STAT5 signalling cascade, promoting survival, proliferation, and differentiation of erythroid precursors into mature red blood cells. PEGylation extends the half-life allowing monthly dosing. The lack of structural similarity to EPO was intended to prevent cross-reactive antibody formation.

What the evidence actually shows

Grade B

Evaluated in PEARL and EMERALD Phase 3 programmes, demonstrating non-inferiority to epoetin alfa in maintaining hemoglobin in CKD patients on dialysis. However, post-marketing surveillance revealed higher-than-expected serious anaphylactic reactions, leading to voluntary withdrawal in 2013. Three deaths attributed to hypersensitivity. Despite withdrawal, clinical data demonstrated proof-of-concept for synthetic peptide-based EPO receptor agonism.

Regulatory status

Status
APPROVED THEN WITHDRAWN. No longer available anywhere.
Approved as
OMONTYS (peginesatide) injection, NDA 202799, FDA-approved 27 March 2012 for the treatment of anaemia due to chronic kidney disease in adult patients ON DIALYSIS. It was explicitly NOT indicated for CKD patients not on dialysis, for cancer patients, or as a substitute for transfusion. Label initial dose: 0.04 mg/kg body weight once monthly. Carried the ESA class boxed warning: 'ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE.'
Clinical stage
Completed Phase 3 (EMERALD and PEARL programmes), approved 2012, recalled 2013, approval withdrawn 2019.
WADA
Prohibited. The WADA Prohibited List section S2.1.1 (EPO-Receptor Agonists) covers erythropoietins, EPO-based constructs and EPO-mimetic agents, and names peginesatide. Prohibited at all times.
Source ↗

Pharmacokinetics

Half-life
1 days
Tmax
2 days
Absorption
subcutaneous
Elimination
renal
Washout
30 days
Titration
Documented as required
Low-confidence pharmacokinetics
These figures are recorded as established rather than measured in a published PK study. Treat them as an order of magnitude. Anything downstream of them — accumulation, steady state, washout — inherits that uncertainty.

Dosing — what backs each figure

Peginesatide (OMONTYS) was FDA approved in March 2012 for anaemia of chronic kidney disease in adults on dialysis, with a labelled starting dose of 0.04 mg/kg intravenously or subcutaneously once monthly, under an ESA class boxed warning. Affymax and Takeda issued a nationwide voluntary recall of all lots in February 2013 after post-marketing reports of serious hypersensitivity reactions including fatal anaphylaxis, and the product was withdrawn; the labelled regimen is recorded here for reference only and the drug is not available.

ClinicalApproved labelling or a published human trial

Handling and storage

No compound-specific stability data exists
The approved product OMONTYS was a ready-to-use solution, not a lyophilised powder. Label: 'The recommended storage temperature is refrigerated at 2 degrees C to 8 degrees C (36 F to 46 F). Protect from light. Retain in carton until time of use.' Where refrigeration was unavailable, vials and prefilled syringes could be held at 25 degrees C or less for up to 30 days. Multiple-use vials were to be returned to 2-8 degrees C after first use and discarded after 28 days. Single-use vials and prefilled syringes were for one use only. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.
→ Reconstitution walkthrough→ Reconstitution calculator

Safety

References (4)

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
pubchemCid, sequence.oneLetter, reconstitution.solvent

Research use only
This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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