Chemistry:Donidalorsen
Donidalorsen, sold under the brand name Dawnzera, is a medication used to prevent attacks of hereditary angioedema.[1] Donidalorsen is a prekallikrein-directed antisense oligonucleotide.[1] It is given by injection under the skin (subcutaneous).[1]
Donidalorsen was approved for medical use in the United States in August 2025,[2] and in the European Union in January 2026.[3][4]
Medical uses
Donidalorsen is indicated for prophylaxis to prevent attacks of hereditary angioedema.[1]
Mechanism of action
Donidalorsen is an antisense oligonucleotide designed to treat hereditary angioedema (HAE) by targeting and reducing the production of prekallikrein (PKK), a key protein involved in triggering inflammatory mediators responsible for HAE attacks. It works by binding to the messenger RNA (mRNA) of the KLKB1 gene, which encodes prekallikrein, and promoting the breakdown of this mRNA. As a result, the synthesis of PKK protein is decreased. Lower PKK levels reduce the downstream production of bradykinin, a potent vasodilator implicated in the swelling episodes characteristic of HAE. Through this RNA-targeted mechanism, donidalorsen lowers the frequency and severity of angioedema attacks by interrupting the pathway responsible for excessive bradykinin generation.[5][6]
Society and culture
Legal status
Donidalorsen was approved for medical use in the United States in August 2025.[7]
In November 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Dawnzera, intended for the routine prevention of recurrent attacks of hereditary angioedema in adults and adolescents aged twelve years of age and older.[3] The applicant for this medicinal product is Otsuka Pharmaceutical Netherlands B.V.[3] Donidalorsen was authorized for medical use in the European Union in January 2026.[3][4]
Names
Donidalorsen is the international nonproprietary name.[8]
Donidalorsen is sold under the brand name Dawnzera.[1]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Cite error: Invalid
<ref>tag; no text was provided for refs namedDawnzera FDA label - ↑ "Dawnzera (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema" (Press release). Ionis Pharmaceuticals, Inc. 21 August 2025. Retrieved 22 August 2025 – via Business Wire.
- ↑ 3.0 3.1 3.2 3.3 "Dawnzera EPAR". 14 November 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/dawnzera. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ 4.0 4.1 "Dawnzera Product information". 9 January 2026. https://ec.europa.eu/health/documents/community-register/html/h2009.htm.
- ↑ "Donidalorsen: An Investigational RNA-targeted Medicine". Ionis Pharmaceuticals, Inc.. https://ionis.com/sites/default/files/pdfs/Donidalorsen_Fact_Sheet_Final.pdf.
- ↑ "Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies". Expert Opinion on Investigational Drugs 33 (3): 191–200. March 2024. doi:10.1080/13543784.2024.2320700. PMID 38366937.
- ↑ "Dawnzera: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=219407.
- ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 86". WHO Drug Information 35 (3). 2021.
Further reading
- "Efficacy and safety of Donidalorsen in Hereditary Angioedema with C1 inhibitor deficiency: a systematic review and a meta analysis". Archives of Dermatological Research 317 (1): 110. December 2024. doi:10.1007/s00403-024-03652-3. PMID 39666085.
External links
- Clinical trial number NCT05139810 for "OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)" at ClinicalTrials.gov
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