Garadacimab is a first‐in‐class, fully human, potent, anti‐activated FXII monoclonal antibody.
Activated factor XII (FXIIa) (1,2):
- is the principal initiator of the kallikrein–kinin system, leading to production of bradykinin, the key inflammatory mediator responsible for vasodilation and vascular permeability
- C1 inhibitor (C1INH) regulates FXIIa in healthy individuals
- C1INH is the main regulator of the kallikrein–kinin system through the inhibition of FXIIa and plasma kallikrein
- in HAE (hereditary angioedema), most patients have C1INH deficiency (HAE‐C1INH‐Type1) or dysfunction (HAE‐C1INH‐Type2), leading to uncontrolled activation of FXII, which increases vascular permeability, resulting in fluid accumulation in the subcutaneous and submucosal tissues
- HEA is a rare genetic disease that manifests as recurrent, unpredictable, and potentially life‐threatening attacks of angioedema
- the subsequent dysregulation of the kallikrein–kinin system results in overproduction of bradykinin, ultimately leading to HAE attacks
- HAE is characterized by recurrent episodes (attacks) of disfiguring swelling, most commonly affecting the skin, gastrointestinal tract, and upper airways; attacks involving the tongue and larynx are potentially life‐threatening
Study evidence shows that Garadacimab has a favorable safety profile suitable for long‐term use and provides durable protection against HAE attacks (2).
NICE suggest that (3):
- Garadacimab can be used as an option to prevent recurrent attacks of hereditary angioedema in people 12 years and over, only if:
- they have 2 or more attacks a month, and
- the company provides garadacimab according to the commercial arrangement
The NICE committee noteL
- "..Usual treatment for recurrent attacks of hereditary angioedema in people 12 years and over is long-term preventive treatment with berotralstat, C1‑esterase inhibitors (C1‑INHs) or lanadelumab...Clinical trial evidence shows that garadacimab reduces the number of hereditary angioedema attacks and increases the likelihood of freedom from attacks compared with placebo. Indirect comparisons suggest that garadacimab's clinical effectiveness is the same or better than berotralstat, C1‑INHs or lanadelumab.."
Reference:
- Staubach P et al. Timing of Onset of Garadacimab for Preventing Hereditary Angioedema Attacks. Clin Exp Allergy. 2024 Dec;54(12):1020-1023.
- Reshef A et al; VANGUARD Study Group. Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open-label extension study. Allergy. 2025 Feb;80(2):545-556.
- NICE (October 2025), Garadacimab for preventing recurrent attacks of hereditary angioedema in people 12 years and over.