A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)

Inclusion Criteria 1. Participants and, as applicable, legally authorized representatives (i.e., parent(s)/legal guardian), must provide written and signed informed consent form (ICF). 2. Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks. Open-Label Extension Participants ONLY: 3. Satisfactory completion of ISIS 721744-CS5 (randomized placebo-controlled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile. New (not previously on donidalorsen) Participants ONLY: 4. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent. 5. Participants must have a documented diagnosis of HAE-1/HAE-2. 6. Participants must be on a stable dose (≥ 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or SC C1-esterase inhibitor prior to the Screening Period. Exclusion Criteria Open-Label Extension Participants: 1. Have any new condition or worsening of an existing condition or change or anticipated change in medication. New (not previously on donidalorsen) Participants ONLY: 2. Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III). 3. Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks. 4. Any clinically-significant abnormalities in screening laboratory values. 5. Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated. 6. Hypersensitivity to the active substance (donidalorsen) or to any of the excipients. 7. Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer. 8. Recent history of, or current drug or alcohol abuse. 9. Participated in a prior donidalorsen study. 10. Exposure to any of the following medications: 1. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption. 2. Oligonucleotides (including small interfering ribonucleic acid \[siRNA\]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines.