Icatibant
Icatibant (Firazyr), bradykinin B2 receptor antagonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: Firazyr, HOE-140, Icatibant acetate
A synthetic decapeptide that blocks the bradykinin B2 receptor, approved in 2011 for acute attacks of hereditary angioedema. It beat tranexamic acid in one phase 3 trial and did not separate from placebo in the other, and in ACE inhibitor angioedema the larger placebo-controlled trial was null.
Overview
Icatibant is a 10 amino acid synthetic peptide built with non-natural amino acids so that proteases cannot break it down, which is what lets a peptide antagonist survive as a subcutaneous injection. It blocks the bradykinin B2 receptor, and since bradykinin is the mediator that produces the swelling in hereditary angioedema, blocking that receptor stops an attack.
The registration evidence is two phase 3 trials. In FAST-2, 74 people with hereditary angioedema attacks were randomised to a single 30 mg subcutaneous injection of icatibant or to oral tranexamic acid, and the median time to clinically significant relief was 2.0 hours versus 12.0 hours (p < 0.001). In FAST-1, 56 people were randomised against placebo and the difference was 2.5 hours versus 4.6 hours, which did not reach significance (p = 0.14); 3 icatibant recipients and 13 placebo recipients needed rescue medication, and the authors argued that early rescue use obscured the comparison. Both trials were funded by Jerini, the developer.
The drug has also been tested outside its licence, and those results are mixed to negative. In ACE inhibitor-induced angioedema, a 2015 phase 2 trial in 27 analysed patients found resolution in a median 8.0 hours with icatibant versus 27.1 hours with prednisolone plus clemastine (p = 0.002), funded by Shire. A larger 2017 trial randomised 121 people to icatibant or placebo and found no difference at all: median time to meeting discharge criteria was 4.0 hours in both groups (p = 0.63). In COVID-19 pneumonia, a randomised open-label phase 2 trial in 73 inpatients missed its primary endpoint.
Regulatory position, verified 11 September 2026 through openFDA: FIRAZYR, NDA 022150, Takeda Pharms USA, original approval 25 August 2011, listed Prescription. Six generic icatibant acetate injections are also listed Prescription, from Teva (2019), Hansoh, Fresenius Kabi and Cipla (2020), Eugia (2023) and Alembic (2024).
Mechanism of action
In humans, icatibant competitively antagonises the bradykinin B2 receptor. In hereditary angioedema, C1 inhibitor deficiency allows uncontrolled kallikrein activity and excess bradykinin, which increases vascular permeability and produces the characteristic swelling; blocking B2 removes the signal that causes the swelling. The same logic applies to ACE inhibitor angioedema, where the enzyme block raises bradykinin. Icatibant treats an attack that is already underway and does nothing to prevent the next one.
Human evidence
Strong for the licensed indication and clearly mixed outside it. Two randomised phase 3 trials in hereditary angioedema, two randomised trials in ACE inhibitor angioedema pointing in opposite directions, and one randomised trial in COVID-19 that missed its primary endpoint.
- FAST-2: 74 people randomised, median time to clinically significant relief 2.0 hours with icatibant versus 12.0 hours with tranexamic acid (p < 0.001). Manufacturer funded.
- FAST-1: 56 people randomised against placebo, 2.5 versus 4.6 hours (p = 0.14). The placebo comparison did not reach significance; 13 of the placebo recipients took rescue medication against 3 on icatibant.
- ACE inhibitor angioedema, 2015 phase 2: 27 analysed, median resolution 8.0 versus 27.1 hours favouring icatibant (p = 0.002), against active standard care rather than placebo.
- ACE inhibitor angioedema, 2017: 121 randomised against placebo across 31 centres, median time to discharge criteria 4.0 hours in both arms (p = 0.63). No secondary endpoint or subgroup favoured icatibant.
- COVID-19 pneumonia, 2023: 73 inpatients, open-label. Primary endpoint missed (73.0 versus 55.6 percent, p = 0.115); a 28 day secondary endpoint and a mortality difference favoured icatibant in a trial not designed or sized to test mortality.
What this does not tell you: The hereditary angioedema evidence is about how fast a single attack resolves, not about how often attacks happen, because icatibant is not a prophylactic. The two ACE inhibitor angioedema trials cannot both be right: the smaller one compared against steroids and antihistamines, the larger one against placebo and found nothing, and the placebo-controlled result is the harder test. The COVID-19 trial was open-label with 73 participants, which makes its secondary and mortality findings hypothesis generating.
Reading the research record
Icatibant is the payoff of the bradykinin story on this site: an endogenous mediator that cannot be used as a drug, whose receptor blocker became one. It is also a useful demonstration that a peptide can be engineered around its own weakness. Natural peptides are destroyed by proteases in minutes; icatibant is built with non-proteinogenic amino acids and survives long enough to be a self-administered subcutaneous injection with a mean elimination half-life of 1.4 hours.
The indication creep is worth watching honestly. ACE inhibitor angioedema is far more common than hereditary angioedema, has no approved treatment, and shares the same mediator, so trying icatibant there was rational. One trial against active standard care favoured it and the larger placebo-controlled trial found nothing, and the systematic review reports exactly that split. The COVID-19 trial follows the same pattern of a plausible mechanism producing a missed primary endpoint with favourable secondary numbers. Neither is a reason to extend the indication, and this page does not.
Six generic icatibant products have been approved in the United States since 2019, which changes the economics: the incentive to fund further trials of an off-patent peptide in a new indication is now small.
The evidence, charted
Fig. 1 · evidence composition
5of 8 citations (63%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 6 distinct years, 2004 to 2023, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Prescription
AU
Prescription
CA
Prescription
Approved in 1 of 4, prescription route in 3, not approved in 0. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2010
Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema
Two phase 3 trials. FAST-2 randomised 74 people against oral tranexamic acid: median time to clinically significant relief 2.0 versus 12.0 hours (p < 0.001). FAST-1 randomised 56 people against placebo: 2.5 versus 4.6 hours (p = 0.14), with 3 icatibant and 13 placebo recipients needing rescue medication. No icatibant-related serious adverse events. Funded by Jerini.
New England Journal of Medicine - Human2015
A randomized trial of icatibant in ACE-inhibitor-induced angioedema
Phase 2, double-blind, double-dummy: 27 patients analysed per protocol. Median time to complete resolution 8.0 hours with icatibant versus 27.1 hours with intravenous prednisolone plus clemastine (p = 0.002). Complete resolution within 4 hours in 5 of 13 versus 0 of 14 (p = 0.02). Funded by Shire.
New England Journal of Medicine - Human2017
Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema
121 adults at 31 centres in 4 countries randomised to icatibant 30 mg or placebo. No difference in time to meeting discharge criteria (median 4.0 hours in both arms, p = 0.63), no difference in time to symptom relief (2.0 versus 1.6 hours, p = 0.57), and no difference in any secondary endpoint or prespecified subgroup. A clean null result in the larger, placebo-controlled test.
Journal of Allergy and Clinical Immunology: In Practice - Review2018
Pharmacotherapy for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review
5 studies covering 218 cases. One of the 2 icatibant studies showed faster improvement than corticosteroids plus antihistamines and the other did not; ecallantide and C1 inhibitor replacement showed no significant benefit over control.
Otolaryngology Head and Neck Surgery - Human2023
Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial
73 inpatients with COVID-19 pneumonia randomised to icatibant plus standard care or standard care alone. The primary endpoint, clinical response at day 10 or discharge, was 73.0 versus 55.6 percent and did not reach significance (p = 0.115). The secondary endpoint at 28 days favoured icatibant (100 versus 83.3 percent, p = 0.011) and no deaths occurred on icatibant versus 6 on control. Open-label and small, with the primary endpoint missed.
Clinical Infectious Diseases - Review2018
Icatibant for the treatment of hereditary angioedema with C1-inhibitor deficiency in adolescents and in children aged over 2 years
Review of the paediatric and adolescent evidence supporting use below adult age, summarising the dosing and safety data available in that population.
Expert Review of Clinical Immunology - Human2010
Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (FAST-1)
Registry record for the placebo-controlled phase 3: 84 participants enrolled, completed, lead sponsor Shire. The companion trial against tranexamic acid, NCT00500656, enrolled 85 and is also completed.
ClinicalTrials.gov - Review2004
Bradykinin receptor ligands: therapeutic perspectives
Review of the kinin receptor pharmacology behind icatibant, written before its approval, describing why B2 antagonism became the drug development route.
Nature Reviews Drug Discovery
Frequently asked questions
What is icatibant approved for?
Acute attacks of hereditary angioedema in adults, by subcutaneous injection. It was approved in the United States on 25 August 2011 and is listed Prescription, along with 6 generics approved between 2019 and 2024.
How fast does it work?
In the phase 3 trials, median time to clinically significant relief was 2.0 hours against 12.0 hours for tranexamic acid, and 2.5 hours against 4.6 hours for placebo. Only the tranexamic acid comparison was statistically significant.
Does it work for angioedema caused by blood pressure drugs?
The evidence conflicts. A 27 patient trial found resolution in 8.0 hours versus 27.1 hours with steroids and antihistamines. A larger 121 patient placebo-controlled trial found no difference at all, median 4.0 hours in both arms. It is not approved for this use.
Does icatibant prevent angioedema attacks?
No. It treats an attack that has started. Prophylaxis of hereditary angioedema uses different medicines, and nothing in the icatibant trial programme tested attack prevention.