GARADACIMAB-GXII INJ,SOLN
Clinical Criteria Summary
Document 902: Garadacimab ANDEMBRY CFU Aug 2026
Exclusion Criteria
- Angioedema or abdominal pain not associated with C1 inhibitor deficiency, including hereditary angioedema with normal C1 inhibitor (HAE nC1-INH)
- Concomitant use with another prophylaxis agent for HAE (e.g., berotralstat, donidalorsen, or lanadelumab)
Inclusion Criteria
- Restricted to VA / VA Community Care allergy/immunology provider, dermatology provider, or locally designated expert
- Diagnosis of Hereditary Angioedema Type 1 or 2 as established by laboratory testing
- Long-term prophylaxis for HAE attacks or short-term prophylaxis prior to procedures or intubation
Laboratory & Diagnostic Criteria
- C4 level below the limit of normal
- C1 inhibitor (C1-INH) antigenic level below the limit of normal OR C1-INH functional level below the limit of normal
- Hereditary angioedema with C1 inhibitor deficiency (types 1 and 2) is a result of SERPING1 variants
- Hereditary angioedema with normal C1 inhibitor (HAE-nC1-INH) is caused by variants in other genes (e.g., FXII, PLG, KNG1, ANGPT1, MYOF, HS3ST6, CPN1, or DAB21P) or unidentified genetic causes
Document 903: MON Garadacimab ANDEMBRY monograph Aug 2026
Indication & Patient Population
- Prophylaxis of hereditary angioedema (HAE) attacks in adult and pediatric patients aged 12 years and older.
- Primarily studied in HAE with C1 inhibitor deficiency (SERPING1 variants).
- Limited data for HAE with normal C1 inhibitor (HAE-nC1-INH); efficacy was inconsistent in patients with PLG variants, while FXII variant patients demonstrated significant attack reduction and prolonged attack-free status.
Dosage & Administration
- Initial loading dose of 400 mg (delivered as two 200 mg injections) subcutaneously (subQ).
- Maintenance dosage of 200 mg subQ every month.
- Available as 200 mg/1.2 mL prefilled autoinjector and prefilled syringe.
Efficacy Considerations
- Significantly reduces HAE attacks with a mean monthly attack rate of 0.2 during treatment (94.9% reduction from baseline).
- 98.2% of patients achieved ≥50% reduction in attack rate; 84.8% achieved ≥90% reduction.
- Median time to first attack after initiation was 2.2 years.
- Achieves clinical significance defined by Angioedema Quality of Life (AE-QoL) Scale, with mean treatment difference in AE-QoL reduction of 26.7 points at month 6.
Safety & Monitoring
- No Boxed Warnings or Contraindications.
- May prolong activated partial thromboplastin time (aPTT) due to assay interaction; not associated with bleeding events.
- Most common adverse events: COVID-19, nasopharyngitis, headache, upper respiratory tract infection, and injection-site erythema.
Pregnancy & Lactation
- No available data on use in pregnant women; potential fetal effects likely greater during the third trimester.
- Animal studies showed no evidence of fetal harm or maternal toxicity at exposures up to 100 times the maximum recommended human dose.
- No data on presence in human milk or effects on breastfed infants.
Place in Therapy & Guideline Recommendations
- Recommended as a first-line option for long-term prophylaxis (LTP) of HAE per the 2025 WAO Guidelines.
- Other first-line LTP options include berotralstat, lanadelumab, donidalorsen, and subQ C1-INH; guidelines do not prefer one first-line agent over another.
- No guideline recommendations specific to HAE-nC1-INH patients, though some have been successfully treated with garadacimab or other therapies.
Patient Selection Criteria
- Therapy selection should be guided by individual patient factors including HAE subtype, ability to self-inject, concomitant medications, and attack characteristics.
- For HAE-nC1-INH patients (particularly those with PLG or FXII variants), tranexamic acid may perform better compared to C1-INH deficiency subtypes.