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Pharvaris

DISEASE FOCUS

Bradykinin-mediated angioedema (AE-BK) is a rare, potentially life-threatening condition characterized by recurrent and unpredictable swelling attacks.

Bradykinin as Key Mediator1-8

AE-BK swelling attacks are generally caused by excess bradykinin binding to the bradykinin B2 receptor of blood vessels, leading to vasodilation and fluid flow into the surrounding tissue.
There are multiple physiological pathways by which bradykinin is produced; abnormalities, such as genetic variants or other underlying conditions, may result in dysregulation of bradykinin production and/or signaling through the bradykinin B2 receptor.
Antagonism of the bradykinin B2 receptor is one way of regulating bradykinin signaling by directly blocking the activity of the main mediator responsible for the swelling attacks.

What is bradykinin?

Bradykinin is a potent, short‑acting peptide involved in inflammation and vascular regulation.
When a condition is bradykinin‑mediated, it means:
  • Bradykinin—not histamine—is the main driver of symptoms
  • The effects are due to increased blood vessel permeability and vasodilation, leading to swelling, pain, and sometimes low blood pressure, rather than allergic reactions

Our Scientific Approach

Explore our scientific approach to bradykinin-mediated diseases
Learn more
Hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor (C1INH) deficiency (AAE-C1INH) are types of bradykinin-mediated angioedema.1,3,6

Hereditary Angioedema10-12

HAE is a complex, rare, life-long genetic condition with significant burden from recurrent, unpredictable, disabling, and potentially life-threatening attacks of swelling affecting various body parts. Common attack locations include the extremities, face and neck, abdomen, and larynx. If untreated, HAE attacks can last multiple days. HAE affects all genders and ethnicities.
Different forms of HAE are currently recognized and genetically identifiable due to their pathogenesis.1,2,6,14,15

Treatment Landscape of HAE1,18-23

Various therapeutic approaches for managing HAE have been investigated and approved, including replacement of C1INH, inhibition of plasma kallikrein, inhibition of activated Factor XII, prevention of prekallikrein synthesis, and antagonism of the bradykinin B2 receptor.
Of these mechanisms, bradykinin B2 receptor antagonism is the only one that acts at the bottom of the bradykinin-forming cascade, thereby regulating bradykinin activity, regardless of the pathway(s) leading to its formation.

Acquired Angioedema due to C1INH Deficiency (AAE-C1INH)1,18-23

The clinical manifestation of AAE-C1INH are the same as HAE—recurrent, unpredictable, disabling, and potentially life-threatening attacks of swelling affecting various body parts—however, the pathogenesis is different.
AAE-C1INH is not genetically caused—it is “acquired” during a person’s life, and is usually secondary to an underlying medical condition, most commonly lymphoproliferative disorders and autoimmune diseases, that consume or neutralize C1INH.25,26

Treatment landscape of AAE-C1INH

There are currently no therapies approved for the management of AAE-C1INH.

Current AE-BK Treatment Options24-28

If untreated, attacks can last up to five days and may spread to other locations before resolving.
Current management focuses on therapies for on-demand treatment (ODT) as well as long-term prophylaxis (LTP). Subcutaneous injections, IV infusions, and oral options are available to people, though trade-offs may be occurring with respect to efficacy, tolerability, and/or convenience.

Unmet needs29,30

Despite the availability of preventative and on-demand therapies, people living with AE-BK may face significant unmet needs. Patients might still endure burdensome administration routes, breakthrough attacks despite prophylactic treatment, and frequent need for multiple doses of on-demand therapies .

Treatment Guidelines1,14,17

According to the 2021 WAO/EAACI guidelines and the US HAEA Medical Advisory Board Guidelines for HAE management, HAE management and treatment goals should follow:

MANAGEMENT

The goals of treatment are to reduce attack duration and severity and achieve total control of the disease 
and to normalize patients’ lives
All patients should have an action plan
for the management of HAE
HAE-specific comprehensive, integrated care should be available for all patients

Patients should be treated by a specialist with specific expertise in managing HAE

PROPHYLAXIS

Patients should be evaluated for LTP at every visit, taking disease activity, burden, and control as well as patient preference into consideration

All patients who are using LTP should be routinely monitored for disease activity, impact, and control to inform optimization of treatment dosages and outcomes

Short-term prophylaxis should be considered before medical, surgical, or dental procedures and other angioedema attack-inducing situations

—

ON-DEMAND

All attacks should be considered for ODT
Attacks should be treated as early as possible
Any attack affecting or potentially affecting the upper airway should be treated
All patients should be educated about triggers that may induce attacks

MANAGEMENT

PROPHYLAXIS

ON-DEMAND

The goals of treatment are to reduce attack duration and severity and achieve total control of the disease and to normalize patients’ lives

Short-term prophylaxis should be considered before medical, surgical, or dental procedures and other angioedema attack-inducing situations

All attacks should be 
considered for ODT

All patients should have 
an action plan for the 
management of HAE

Patients should be evaluated for LTP at every visit, taking disease activity, burden, and control as well as patient preference into consideration

Attacks should be treated 
as early as possible

HAE-specific comprehensive, integrated care should be available for all patients

All patients who are using LTP should be routinely monitored for disease activity, impact, and control to inform optimization of treatment dosages 
and outcomes

Any attack affecting or potentially affecting the upper airway should 
be treated

Patients should be treated by a specialist with specific expertise in managing HAE

All patients should be 
 educated about triggers 
 that may induce attacks

References

1. Maurer M, et al. Allergy. 2022;77:1961-1990; 2. Zuraw BL, et al. Clin Rev Allergy Immunol. 2025;68(1):24; 3. Busse PJ et al. N Engl J Med. 2020; 2020;382:1136-1148; 4. Drouet C, et al. Front Allergy. 2022;3:835503; 5. Germenis AE, et al. J Allergy Clin Immunol Pract. 2020;8(3):901-911; 6. Reshef A, et al. J Allergy Clin Immunol. 2024;154(2):398-411.e1; 7. Smith TD and Riedl MA. Ann Allergy Asthma Immunol. 2024;133(4):380-390; 8. D'Apolito M, et al. J Allergy Clin Immunol. 2024;154(3):698-706; 9. Lima A, et al. Frontiers in Allergy. 2023; 1263432; 10. Abdulkarim A and Craig TJ. Hereditary Angioedema. 2023. https://www.ncbi.nlm.nih.gov/books/NBK482266/. Last accessed June 2026; 11. Bork K, et al. J Allergy Clin Immunol. 2021;148:1041-1048; 12. Mendivil J, et al. Orphanet J Rare Dis. 2021;16(1):94; 13. Longhurst HJ and Bork K. Br J Hosp Med. 2019;80(7):391-398; 14. Busse PJ, et al. J Allergy Clin Immunol Pract. 2021;9:132-150; 15. Canadian/International guidelines Betschel S et al. Allergy Asthma Clin Immunol. 2026; 16. Betschel S, et al. Allergy Asthma Clin Immunol. 2019;15:72; 17. Vazquez DO et al. World Allergy Organ J. 2026;19; 18. Cicardi et al. Allergy Asthma Clin Immunol. 2010; 19. Otani IM et al. Immunol Allergy Clin North Am. 2017; 20. Petersen RS et al. J Allergy Clin Immunol. 2024; 21. de Lange M et al. J Allergy Clin Immunol. 2025; 22. Morsi H et al. Clin Exp Immunol. 2025; 23. Toprak ID. Front Immunol. 2026; 24. MacGinnitie AJ. Pediatr Allergy Immunol. 2014;25:420-427; 25. Banerji A, et al. Ann Allergy Asthma Immunol. 2013;111:329-336; 26. Bernstein JA, et al. Int J Emerg Med. 2017;10:15; 27. Manning ME. Allergy Asthma Proc. 2020;41(Suppl 1):S22-S25; 28. Zuraw BL. N Engl J Med. 2008;359:1027-1036; 29. Bernstein JA, et al. J Manag Care Spec Pharm. 2020;26(2);203-210; 30. Food and Drug Administration. The voice of the patient - Hereditary angioedema. Published May 2018. Accessed June, 2026. https://www.fda.gov/files/about fda/published/The-Voice-of-the-Patient---Hereditary-Angioedema.pdf