Donidalorsen

Donidalorsen is an ASO‑GalNAc conjugate that causes ribonuclease H1 (RNase H1)‑mediated degradation of PKK mRNA through binding to PKK mRNA, which results in reduced production of PKK protein. PKK is a pro‑enzyme for plasma kallikrein, which results in the release of bradykinin, a potent vasodilator causing swelling and pain in HAE.

• DAWNZERA™ is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is a prekallikrein directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.

• DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA [see Warnings and Precautions (5.1) and Adverse Reactions (6) ] . History of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.contraindicated

The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg every 8 weeks may also be considered. ( 2.1 ) See full prescribing information for administration instructions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg administered subcutaneously every 8 weeks may be considered. Missed Dose(s) If a dose of DAWNZERA is missed, administer DAWNZERA as soon as possible. Resume treatment at the recommended dosing frequency from the date of the most recently administered dose. 2.2 Administration Instructions For subcutaneous use. DAWNZERA is intended for self-administration or administration by a caregiver. Prior to treatment initiation, train patients and/or caregivers on proper preparation and subcutaneous administration technique of DAWNZERA autoinjector [see Instructions for Use ] . Remove the single‑dose autoinjector from the refrigerator 30 minutes prior to the injection and allow to warm to room temperature. Do not use other warming methods. Inspect DAWNZERA visually for particulate matter and discoloration prior to administration. The solution should appear clear and colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed prior to administration. Administer DAWNZERA subcutaneously into the abdomen or upper thigh region. The back of the upper arm can also be used as an injection site if a caregiver or healthcare provider administers the injection.

Hypersensitivity reactions including anaphylaxis have been reported following use of DAWNZERA. Advise patients to discontinue DAWNZERA and seek immediate medical attention if serious hypersensitivity reactions occur. ( 5.1 ) 5.1 Risk of Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA [see Adverse Reactions (6.1) ] . If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Risk of Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ionis Pharmaceuticals at 1-833-644-6647 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DAWNZERA reflects the exposure in a total of 171 adult and pediatric patients 12 years and older with hereditary angioedema (HAE) from a placebo-controlled trial (OASIS-HAE) [see Clinical Studies (14) ] , and 2 other clinical studies. The average duration of DAWNZERA treatment exposure across the 3 clinical studies was 14 months. The safety data below is based on the 24-week multicenter, randomized, double-blind, placebo-controlled trial (OASIS-HAE), in which patients received at least one subcutaneous dose of DAWNZERA 80 mg once every 4 weeks (n=45), DAWNZERA 80 mg once every 8 weeks (n=23), or matching placebo (n=22). Demographics of the patients in OASIS-HAE are summarized in Clinical Studies [see Clinical Studies (14) ] .

Hepatic Impairment: Use in patients with moderate and severe hepatic impairment is not recommended. ( 8.7 ) 8.1 Pregnancy Risk Summary There are no available data on DAWNZERA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneous administration of donidalorsen or a pharmacologically active mouse‑specific surrogate in a combined fertility and embryo‑fetal development study in mice and a pre‑ and postnatal development study in mice with F0 parental doses up to 5 times the maximum recommended human dose (MRHD, 80 mg) on a body surface area (BSA, mg/m 2 ) basis did not result in any adverse effects on embryofetal development, or behavioral, fertility, and reproductive development in the F1 offspring. Donidalorsen does not cross the placental barrier (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

The pharmacokinetic properties of DAWNZERA were evaluated following subcutaneous administration of multiple doses every 4 weeks in healthy subjects and every 4 weeks or every 8 weeks in patients with HAE. The pharmacokinetics of DAWNZERA were similar between healthy subjects and patients with HAE.

• Aug 21, 2025NDANDA219407Ionis Pharms Inc

1. 1Hereditary Angioedema6441%
2. 2Injection Site Pain1610%
3. 3Abdominal Distension127.6%
4. 4Headache106.4%
5. 5Nausea85.1%
6. 6Swelling85.1%
7. 7Abdominal Pain74.5%
8. 8Injection Site Erythema74.5%
9. 9Peripheral Swelling74.5%
10. 10Product Dose Omission Issue74.5%
11. 11Dizziness53.2%
12. 12Fatigue53.2%
13. 13Injection Site Rash53.2%
14. 14Upper Respiratory Tract Infection53.2%
15. 15Abdominal Discomfort42.5%

The 7 most recently updated of 7 ClinicalTrials.gov registrations naming Donidalorsen as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Donidalorsen Treatment in Children With Hereditary Angioedema
  Recruiting · Phase 3 · Interventional · 20 enrolled · Ionis Pharmaceuticals, Inc.
  NCT07298447updated 2026-05-28
• An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema
  Completed · Phase 2 · Interventional · 20 enrolled · Ionis Pharmaceuticals, Inc.
  NCT04307381updated 2026-05-08
• A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
  Active not recruiting · Phase 3 · Interventional · 154 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05392114updated 2025-12-12
• Donidalorsen Expanded Access Program for Patients With Hereditary Angioedema
  Available · Expanded access · Ionis Pharmaceuticals, Inc.
  NCT06415448updated 2025-07-11
• OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 91 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05139810updated 2025-03-06
• A Study to Assess the Clinical Efficacy of Donidalorsen (Also Known as IONIS-PKK-LRx and ISIS 721744) in Participants With Hereditary Angioedema
  Completed · Phase 2 · Interventional · 23 enrolled · Ionis Pharmaceuticals, Inc.
  NCT04030598updated 2023-04-03
• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen (IONIS-PKK-LRx) Administered Subcutaneously to Healthy Volunteers
  Completed · Phase 1 · Interventional · 32 enrolled · Ionis Pharmaceuticals, Inc.
  NCT03263507updated 2022-08-04

Frequently asked questions

How does Donidalorsen work?

Donidalorsen is an ASO‑GalNAc conjugate that causes ribonuclease H1 (RNase H1)‑mediated degradation of PKK mRNA through binding to PKK mRNA, which results in reduced production of PKK protein. PKK is a pro‑enzyme for plasma kallikrein, which results in the release of bradykinin, a potent vasodilator causing swelling and pain in HAE.

What is Donidalorsen used for?

According to FDA labeling, Donidalorsen carries indications including: DAWNZERA™ is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is a prekallikrein directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Donidalorsen?

Donidalorsen is classified as Drugs used in hereditary angioedema, Gene Expression Interactions, Decreased Bradykinin Activity, Decreased Protein Synthesis, Decreased Vascular Permeability.

What are the brand names for Donidalorsen?

Donidalorsen is marketed under brand names including Dawnzera.

What are the contraindications for Donidalorsen?

Donidalorsen labeling lists contraindications including: DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA [see Warnings and Precautions (5.1) and Adverse Reactions (6) ] . History of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.. Always consult the full prescribing information and a clinician.