DONIDALORSEN INJ,SOLN
Clinical Criteria Summary
Document 901: Donidalorsen DAWNZERA 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, garadacimab, or lanadelumab)
- Moderate or severe hepatic impairment (Child-Pugh class B or C)
Inclusion Criteria
- 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
- Restricted to VA / VA Community Care allergy/immunology provider, dermatology provider, or locally designated expert
Diagnostic Laboratory Requirements
- C4 level below the limit of normal and one of the following: C1 inhibitor (C1-INH) antigenic level below the limit of normal or C1-INH functional level below the limit of normal
Document 900: MON Donidalorsen DAWNZERA monograph Aug 2026
Indication & Patient Population
- Prophylaxis of hereditary angioedema (HAE) attacks in adult and pediatric patients aged 12 years and older.
- Specifically studied in patients with HAE type 1 or 2 (C1 inhibitor deficiency/SERPING1 variants).
- Not studied in patients with HAE with normal C1 inhibitor (HAE-nC1-INH).
Dosage & Administration
- 80 mg subcutaneous every 4 weeks.
- 80 mg every 8 weeks may be considered.
- Dosing interval extensions are based on being attack-free.
- Dose increase to 100 mg is based on inadequate control on 80 mg every 4 weeks.
- Available as an 80 mg/0.8 mL single-dose autoinjector.
Safety, Contraindications & Warnings
- Contraindicated in patients with a history of serious hypersensitivity reactions to donidalorsen or any of its excipients.
- Serious hypersensitivity reactions, including anaphylaxis, have been reported; treatment should be discontinued if these occur.
- Can cause reductions in platelet count (no major bleeding events were observed in trials).
- Increases in liver enzymes (ALT, AST, and GGT) were reported.
Special Populations
- Pregnancy: No available human data regarding use in pregnancy. Animal studies showed no adverse developmental effects at exposures up to 5 times the maximum recommended human dose.
- Lactation: No data on the presence of the drug in human milk.
Place in Therapy & Guideline Recommendations
- Recommended as a first-line option for long-term prophylaxis (LTP) per the 2025 WAO Guidelines.
- Other first-line LTP options include berotralstat, lanadelumab, garadacimab, and subcutaneous C1-INH.
- Guidelines do not preference any one of the first-line agents over another.
- Individual patient factors including HAE subtype, ability to self-inject, concomitant medications, and attack characteristics should guide therapy selection.
Efficacy Considerations
- Demonstrated statistically significant reduction in HAE attack rates compared to placebo in phase 2 and 3 studies.
- Efficacy demonstrated in patients switching from prior LTP agents (lanadelumab, berotralstat, or C1 inhibitor).
- Therapies achieving ≥50% attack rate reduction generally meet or exceed the minimal clinically important difference for Angioedema Quality of Life (AE-QoL) improvement.