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The first kallikrein inhibitor approved for hereditary angioedema — a 60-residue Kunitz domain evolved by phage display.
Also known as: DX-88 · Kalbitor · EPI-KAL-2
Part of the Foundational & therapeutic peptides cluster
Overview
Ecallantide (DX-88, Kalbitor) is a 60-amino-acid recombinant peptide (C305H442N88O91S8, ≈7,054 Da) that inhibits human plasma kallikrein, the enzyme that releases bradykinin. Produced in Pichia pastoris and discovered by phage display, it was FDA-approved in 2009 for acute attacks of hereditary angioedema in patients 16 and older, extended to age 12 in 2014. In the phase 3 EDEMA3 and EDEMA4 trials, a single 30 mg subcutaneous dose improved symptom scores at 4 hours versus placebo.
Source & context
Biological / chemical source: Recombinant 60-residue protein produced in the yeast Pichia pastoris, identified by phage display
Primary research or clinical context: Approved (FDA 2009) for acute attacks of hereditary angioedema in patients aged 12 and older
What ecallantide is
Ecallantide is a 60-amino-acid recombinant peptide that inhibits human plasma kallikrein (KLKB1). It was identified through Dyax's phage-display technology as one of a series of small-protein kallikrein inhibitors and is produced in the yeast Pichia pastoris (IUPHAR record; Lehmann, Current Opinion in Investigational Drugs 2006). PubChem gives the formula C305H442N88O91S8 and an average mass of about 7,054 Da; the eight sulfurs reflect the cysteine-rich Kunitz-domain fold that holds the inhibitory loop in place. It was developed as DX-88 and is marketed as Kalbitor. At 60 residues it sits at the boundary between peptide and small protein; the LactMed database describes it as a large protein molecule of about 7,000 Da.
Mechanism: cutting off bradykinin at its source
Hereditary angioedema (HAE) is caused by deficiency of functional C1-esterase inhibitor, which leaves plasma kallikrein under-regulated. Kallikrein cleaves high-molecular-weight kininogen to release bradykinin, which increases vascular permeability and produces the episodic, non-histaminergic swelling of skin, gut and airway that defines the disease (Kaplan, Chemical Immunology and Allergy 2014; Duffey & Firszt, Journal of Blood Medicine 2015). By binding kallikrein and blocking its enzymatic activity, ecallantide prevents the conversion of kininogen to bradykinin and so reduces the tissue swelling (IUPHAR mechanism record; Martello et al., American Journal of Health-System Pharmacy 2012). Icatibant, on this site, blocks the same pathway one step later at the bradykinin B2 receptor.
Clinical evidence: the EDEMA programme
Ecallantide was studied in three phase II and two phase III trials known collectively as EDEMA (Evaluation of DX-88's Effect in Mitigating Angioedema) (Martello et al., 2012). In the randomised, double-blind, placebo-controlled, multicentre phase III trial EDEMA3, the mean symptom response at 4 hours on the Treatment Outcome Score (the primary endpoint) was significantly greater with a single subcutaneous dose of ecallantide 30 mg than with placebo in patients with acute, moderate-to-severe attacks, and the change in the Mean Symptom Complex Severity scale was also significantly greater. In the similarly designed EDEMA4 trial, both the MSCS change (primary endpoint) and the TOS at 4 hours were significantly greater with ecallantide (Garnock-Jones, Drugs 2010). Phase III trials found it superior to placebo at any anatomical site of attack.
| Trial | Primary endpoint | Result at 4 hours |
|---|---|---|
| EDEMA3 | Treatment Outcome Score | Significantly greater than placebo |
| EDEMA4 | Mean Symptom Complex Severity change | Significantly greater than placebo |
Safety profile
In EDEMA3 and EDEMA4, subcutaneous ecallantide 30 mg was generally well tolerated; adverse events were mostly mild to moderate (Garnock-Jones, 2010). The most common adverse effects are gastrointestinal effects, headache and injection-site reactions; the most severe are the risk of anaphylaxis and the possible development of anti-ecallantide antibodies, and the FDA approved a Risk Evaluation and Mitigation Strategy programme to help ensure safe use (Martello et al., 2012). LactMed notes that no information is available on use during breastfeeding, that milk levels are likely very low given the molecule's size, and that caution is advised especially with newborn or preterm infants.
Regulatory status as of September 2026
Ecallantide was approved by the FDA in 2009 for acute attacks of hereditary angioedema in patients aged 16 and older (Stolz & Horn, Drugs of Today 2010; Zuraw et al., Nature Reviews Drug Discovery 2010), and as of April 2014 may be given to children aged 12 and older (IUPHAR clinical-use record). Development for reduction of peri-operative blood loss during cardiopulmonary bypass was planned but delayed pending partnership negotiations (Lehmann, 2006). ClinicalTrials.gov lists 13 studies, including the completed phase 3 EDEMA trials, a terminated phase 2 study in ACE-inhibitor-induced angioedema, and a withdrawn paediatric tolerability study. It is a prescription medicine administered under medical supervision; this page is educational only.
How it relates to other peptides on this site
Bradykinin is the peptide ecallantide prevents from being made; icatibant is the bradykinin receptor antagonist used for the same disease. Aprotinin, the bovine Kunitz-domain protease inhibitor, is the structural ancestor of the Kunitz-fold approach and is also on this site. Together they illustrate two ways to shut down one pathway: inhibit the enzyme or block the receptor.
Sequence
One-letter sequence commonly cited for Ecallantide (educational; isoforms and modifications may differ):
EAMHSFCAFKADDGPCRAAHPRWFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRD
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 60-residue Kunitz-type inhibitor domain (recombinant, yeast-expressed); six cysteines forming three disulfides
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C305H442N88O91S8
- Average reference mass
- ≈ 7,054
- Receptors
- Enzyme target: plasma kallikrein (KLKB1) — reversible inhibitor, not a receptor ligand
- Backbone
- 60-residue Kunitz-type inhibitor domain (recombinant, yeast-expressed); six cysteines forming three disulfides
- Status
- Approved: FDA (2009) for acute HAE attacks, ages ≥16; extended to ≥12 in 2014. Carries a boxed anaphylaxis warning and a REMS programme
- PubChem CID: 44152182
- IUPHAR ligand: 6955
- ChEMBL: CHEMBL1201837
- CAS RN: 460738-38-9
- UNII: 5Q6TZN2HNM
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 13 registered studies with “Ecallantide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT01832896 | Study to Assess the Tolerability and Safety of Ecallantide in Children and Adolescents With Hereditary Angioed | Phase 2 | withdrawn | 2023-03-31 |
| NCT00262080 | Efficacy and Safety Study of DX-88 to Treat Acute Attacks of Hereditary Angioedema (HAE) | Phase 3 | completed | 2021-06-11 |
| NCT01343823 | Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema | Phase 2 | terminated | 2021-06-11 |
| NCT01059526 | Observational Safety Study for KALBITOR (Ecallantide) in the Treatment of Acute Attacks of Hereditary Angioede | — | completed | 2021-06-08 |
| NCT00457015 | Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE) | Phase 3 | completed | 2021-06-08 |
| NCT00456508 | Safety and Efficacy Study of Repeated Doses of DX-88 (Ecallantide) to Treat Attacks of Hereditary Angioedema ( | Phase 3 | completed | 2021-06-08 |
Ecallantide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 60-residue Kunitz-type inhibitor domain (recombinant, yeast-expressed); six cysteines forming three disulfidesAverage reference mass: 7,054 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 6955 and PubChem CID 44152182.
- TrialsClinicalTrials.gov snapshot added: 13 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Ecallantide
What is Ecallantide?+
Ecallantide (DX-88, Kalbitor) is a 60-amino-acid recombinant peptide (C305H442N88O91S8, ≈7,054 Da) that inhibits human plasma kallikrein, the enzyme that releases bradykinin. Produced in Pichia pastoris and discovered by phage display, it was FDA-approved in 2009 for acute attacks of hereditary angioedema in patients 16 and older, extended to age 12 in 2014. In the phase 3 EDEMA3 and EDEMA4 trials, a single 30 mg subcutaneous dose improved symptom scores at 4 hours versus placebo.
What Canadian product status is recorded for Ecallantide?+
Canadian product status for Ecallantide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Ecallantide?+
Ecallantide is commonly described as approximately 60 amino acids (Recombinant plasma kallikrein inhibitor (Kunitz-domain peptide)).
What is ecallantide?+
A 60-residue recombinant peptide (DX-88, Kalbitor) that inhibits plasma kallikrein, blocking bradykinin release. It is approved for acute attacks of hereditary angioedema.
Is ecallantide approved?+
Yes — FDA-approved in 2009 for acute HAE attacks in patients 16 and older, extended to age 12 in 2014.
How does ecallantide work?+
By reversibly inhibiting plasma kallikrein, the enzyme that converts kininogen to bradykinin; less bradykinin means less vascular leakage and swelling.
What are ecallantide's main risks?+
Anaphylaxis and anti-drug antibodies are the most serious; a REMS programme governs its use. Common effects are gastrointestinal symptoms, headache and injection-site reactions.
How is ecallantide different from icatibant?+
Ecallantide inhibits the enzyme that makes bradykinin; icatibant blocks the bradykinin B2 receptor. Both treat acute HAE attacks.
Related peptides
References & further reading
- 1.Garnock-Jones KP (2010). Ecallantide: in acute hereditary angioedema. Drugs
- 2.Martello JL et al. (2012). Ecallantide for treatment of acute attacks of hereditary angioedema. Am J Health Syst Pharm
- 3.Stolz LE, Horn PT (2010). Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema. Drugs Today (Barc)
- 4.Zuraw B et al. (2010). Ecallantide. Nat Rev Drug Discov
- 5.Duffey H, Firszt R (2015). Management of acute attacks of hereditary angioedema: role of ecallantide. J Blood Med
- 6.Kaplan AP (2014). Bradykinin-mediated diseases. Chem Immunol Allergy
- 7.Lehmann A (2006). Ecallantide (Dyax/Genzyme). Curr Opin Investig Drugs
- 8.PubChem — compound summary for Ecallantide (CID 44152182)