The first and only RNA-targeted treatment for HAE1,2

DAWNZERA is an antisense oligonucleotide (ASO) that binds to plasma PKK mRNA to limit protein production at the source–in the liver, where it is made.1,3,4

DAWNZERA works in 3 steps1,2,5

  1. Step 1

    DAWNZERA is selectively targeted to the liver

  2. Step 2

    DAWNZERA binds to plasma PKK mRNA and directs its degradation

  3. Step 3

    DAWNZERA reduces the production of plasma PKK protein, reducing the overproduction of bradykinin and swelling that characterizes HAE attacks

Graphic showing the mechanism of action of DAWNZERA. Graphic showing the mechanism of action of DAWNZERA.

What is antisense technology?  

Antisense oligonucleotides (ASOs) are designed to bind precisely to RNA and can promote RNA degradation or alter RNA processing to reduce or modify the production of disease-associated proteins.7

Characteristics of ASOs:

  • Targets RNA specifically7

  • Binds to complementary mRNA sequence7

  • Reversible effects7

  • Chemically modified to be stable8

  • Unlike mRNA vaccines, not designed to encode proteins7,9,10

  • Modulates gene expression and targets disease differently compared with small molecules and biologics4,11

mRNA=messenger RNA; RNA=ribonucleic acid.

DAWNZERA restores balance in the kallikrein-kinin pathway1,2,5,12

In HAE type 1 and 2, C1-INH deficiency or dysfunction leads to excess bradykinin production and swelling via the kallikrein-kinin pathway. DAWNZERA targets plasma PKK mRNA to reduce protein production and restore balance.2

MOA -Modal MOA-mobile-modal

C1-INH=C1-inhibitor; HAE=hereditary angioedema; HMWK=high-molecular-weight kininogen; mRNA=messenger RNA; PKK=prekallikrein.

DAWNZERA reduces PKK production and does not edit DNA2,6

DNA=deoxyribonucleic acid; HAE=hereditary angioedema; mRNA=messenger RNA; PKK=prekallikrein; RNA=ribonucleic acid.

See other areas to explore for DAWNZERA:

View long-term efficacy View dosing information

IMPORTANT SAFETY INFORMATION & INDICATION

CONTRAINDICATIONS

DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA. If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort.

INDICATION

DAWNZERA (donidalorsen) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.

Please see full Prescribing Information for DAWNZERA.

References: 1. DAWNZERA. Prescribing information. Ionis Pharmaceuticals. 2. Riedl MA, Bordone L, Revenko A, et al. Clinical progress in hepatic targeting for novel prophylactic therapies in hereditary angioedema. J Allergy Clin Immunol Pract. 2024;12(4):911-918. doi:10.1016/j.jaip.2023.12.025 3. Riedl MA, Tachdjian R, Lumry WR, et al. Efficacy and safety of donidalorsen for hereditary angioedema. N Engl J Med. 2024;391(1):21-31. doi:10.1056/NEJMoa2402478 4.Yu AM, Jian C, Yu AH, et al. RNA therapy: are we using the right molecules? Pharmacol Ther. 2019;196:91-104. doi:10.1016/j.pharmthera.2018.11.011 5. Smith TD, Riedl MA. The future of therapeutic options for hereditary angioedema. Ann Allergy Asthma Immunol. 2024;133(4):380-390. doi:10.1016/j.anai.2024.04.029 6. Ferrone JD, Bhattacharjee G, Revenko AS, et al. IONIS-PKKRx a novel antisense inhibitor of prekallikrein and bradykinin production. Nucleic Acid Ther. 2019;29(2):82-91. doi:10.1089/nat.2018.0754 7. Paunovska K, Loughrey D, Dahlman JE. Drug delivery systems for RNA therapeutics. Nat Rev Genet. 2022;23(5):265-280. doi:10.1038/s41576-021-00439-4 8. Zhang C, Zhang B. RNA therapeutics: updates and future potential. Sci China Life Sci. 2023;66(1):12-30. doi:10.1007/s11427-022-2171-2 9. Szukowska A, Żuk M, Sztompke J, et al. Application of antisense oligonucleotides as an alternative approach for gene expression control and functional studies. Int J Mol Sci. 2025;26(21):10524. doi: 10.3390/ijms262110524 10. Pardi N, Hogan MJ, Porter FW, et al. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261-279. doi:10.1038/nrd.2017.243
11. Tambuyzer E, Vandendriessche B, Austin CP, et al. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov. 2020;19(2):93-111. doi:10.1038/s41573-019-0049-9 12. Diep JK, Liu M, Singh P, et al. Population pharmacokinetic/pharmacodynamic modeling of donidalorsen, an antisense oligonucleotide in development for prophylaxis of hereditary angioedema. CPT Pharmacometrics Syst Pharmacol. 2026;15(2):e70206. doi:10.1002/psp4.70206