Disease Focus - bradykinin-mediated diseases

People living with HAE want to live a normal life.

Despite the substantial progress made in the past two decades,1 people living with HAE still have significant unmet need.2 They compromise between an effective therapy, its safety, or the ease of administration.3,4,5

Regardless of on-demand treatment or attack prevention, patients still experience stress, depression, and anxiety around their next attack.6 The burden of painful injections and the need for multiple doses to provide symptom relief results in 30-40% of HAE attacks not being completely resolved.7

*Footnotes

Hereditary Angioedema

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disease that occurs in approximately 1 in 10,000 to 1 in 50,000 people, according to HAEi.

RARE
1 IN 10,000 – 50,000*

  • USA 7,000-15,000* people
  • EU 9,000-15,000* people
  • Japan 2,500-4,500* people

GENETIC
ENZYME DEFICIENCY

Decreased production or production of functionally impaired C1 esterase inhibitor (C1-INH)

HEREDITARY
INHERITED

Generally passed on from parents to children

*Ghazi A, Grant JA. Hereditary angioedema: epidemiology, management, and role of icatibant. Biologics. 2013;7:103-13. doi: 10.2147/BTT.S27566. Epub 2013 May 3. PMID: 23662043; PMCID: PMC3647445.

Living with HAE

IMPACT

  • Unpredictable and prolonged swelling attacks
  • Extremely painful
  • Limiting daily activity
  • Stress-related

LOCATION

  • Upper and lower limbs
  • Facial area
  • Gastrointestinal tract
  • Extremities
  • Genitals
  • Airways

SEVERITY

  • Frequency is personal and could change throughout the course of a person’s life; it can vary from one attack per year to multiple attacks per week
  • Severity of attacks range from mild to severe

SYMPTOMS

  • Severe swelling and pain
  • Nausea
  • Diarrhea
  • Vomiting
  • Airway blockage (potentially life-threatening)

Treatment Landscape

Treatment of HAE consists of long-term prophylaxis, management of acute attacks, and intermittent episodic prophylaxis in advance of known triggers.

Multiple therapies are available, acting at different points in the bradykinin-forming cascade. Only one approved therapy, icatibant, acts directly at the bradykinin B2 receptor to treat all types of HAE by inhibiting bradykinin interaction with its bradykinin B2 receptor target, and hence by putting a halt to bradykinin-mediated signaling.

All current therapies, including icatibant, are limited by invasive routes of drug administration (injection or infusion), inconvenient dosing regimens, or undesired side effects. Surveys of people living with HAE overwhelmingly show that they seek additional treatment options.

A best-in-class, oral small-molecule antagonist of the bradykinin B2 receptor may provide an effective and more convenient way to manage HAE and improve quality of life. Pharvaris aims to bring oral options that meet the needs of people with HAE.

Deucrictibant is designed to directly target the ultimate event in the HAE cascade, the interaction of bradykinin with the bradykinin B2 receptor, a proven mechanism for the treatment of HAE attacks.

OUR PIPELINE

Bradykinin Mediation

Hereditary angioedema (HAE) is a bradykinin-mediated disease. Blocking bradykinin shuts down the swelling attack, as shown by over a decade of patient experience with icatibant, an injectable therapy.

Bradykinin has a high affinity and high agonist potency at the bradykinin B2 receptor but has a nearly 1000-fold lower affinity and potency at the bradykinin B1 receptor, making it a selective B2 agonist. Bradykinin activates the bradykinin B2 receptor, resulting in increased permeability of blood vessels, release of fluid into surrounding tissue and edema (swelling). Multiple pathological conditions can result in the overabundance of bradykinin. Blocking excess bradykinin signaling through its B2-receptor will inhibit all aberrant bradykinin activity in all circumstances.

OUR SCIENCE

1 Fijen LM, et al. Current and Prospective Targets of Pharmacologic Treatment of Hereditary Angioedema Types 1 and 2. Clinic Rev Allerg Immunol 2021;61:66–76.
2 Maurer M, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. World Allergy Organ J 2022;15(3):100627.
3 Banerji A, et al. Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Ann Allergy Asthma Immunol 2020;124(6):600-607.
4 Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol 2013;111(5):329-336.
5 Bork K, et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol 2021;17:40.
6 Savarese , et al. Psychology and hereditary angioedema: A systematic review. Allergy Asthma Proc 2021;42(1):e1–e7.

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