Mode of action
Mode of action ASO technology
An upclose photo of a neon sign reading 'Get HAE under control'. An upclose photo of a neon sign reading 'Get HAE under control'.

RNA Technology There’s now an RNA-targeted treatment for HAE

DAWNZERA mode of action

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

Text reading 'First and Only'

DAWNZERA is an antisense oligonucleotide (ASO) that binds to prekallikrein (PKK) mRNA to limit plasma protein production at the source—in the liver, where it’s made1,3

Text reading 'First and Only'

1. DAWNZERA is selectively targeted to the liver1,2,4

Graphic showing the mechanism of action of DAWNZERA.

2. DAWNZERA binds to PKK mRNA and directs its degradation1,2,4

Graphic showing the mechanism of action of DAWNZERA.

3. DAWNZERA reduces the production of PKK protein, reducing the release of bradykinin. This prevents the vascular leakage that characterizes HAE attacks1,2,4

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

DAWNZERA has the selectivity of RNA technology and does not irreversibly edit DNA2,5

DNA=deoxyribonucleic acid; mRNA=messenger ribonucleic acid.

ASO technology

What is antisense technology?

Antisense oligonucleotides (ASOs) are a type of RNA-targeted therapy that can interfere with translation of specific proteins. They are designed to bind precisely with RNA and can either degrade or modify disease-causing proteins.6

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    Specifically target RNA6

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    Bind to complementary mRNA sequence7

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    Effects are reversible7

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    Leads to inhibiting gene expression or altering splicing7

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    Chemically modified to be stable: resist degradation by nucleases7

ASOs modulate gene expression and target different aspects of disease-causing proteins than small molecules and biologics6

A graph showing ASOs modulate gene expression and target different aspects of disease-causing proteins. A graph showing ASOs modulate gene expression and target different aspects of disease-causing proteins.

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. 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 5. 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. 6. 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 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. 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