Donidalorsen

CAS 2304692-48-4

분자량 Mw	8672.64
화학식Mf	C296H435N83O151P20S15

ISIS 721744, ISIS-721744

FDA 8/21/2025, Dawnzera, To prevent attacks of hereditary angioedema

DNA, D((2′-O-(2-METHOXYETHYL))M5RU-SP-(2′-O-(2-METHOXYETHYL))RG-SP-(2′-O-(2-METHOXYETHYL))M5RC-(2′-O-(2-METHOXYETHYL))RA-(2′-O-(2-METHOXYETHYL))RA-SP-G-SP-T-SP-M5C-SP-T-SP-M5C-SP-T-SP-T-SP-G-SP-G-SP-M5C-SP-(2′-O-(2-METHOXYETHYL))RA-(2′-O-(2-METHOXYETHYL)

• WHO 11653
• DNA, d((2′-O-(2-methoxyethyl))m5rU-sp-(2′-O-(2-methoxyethyl)(rG-sp-(2′-O-(2- methoxyethyl))m5rC-(2′-O-(2-methoxyethyl))rA-(2′-O-(2-methoxyethyl))rA-spG-sp-T-sp-m5C-sp-T-sp-m5C-sp-T-sp-T-sp-G-sp-G-sp-m5C-sp-(2′-O-(2-methoxyethyl))rA-(2′-O-(2-methoxyethyl))rA-(2′-O-(2-methoxyethyl))rA-sp-(2′-O-(2-methoxyethyl))m5rC-sp-(2′-O-(2-methoxyethyl))rA), 5′-(26-((2-(acetylamino)-2-deoxy-beta-D-galactopyranosyl)oxy)-14,14-bis((3-((6-((2-(acetylamino)-2-deoxybeta-D-galactopyranosyl)oxy)hexyl)amino)-3-oxopropoxy)methyl)-8,12,19-trioxo16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate)
• UNII-ZD4D8M32TL

Ingredient	UNII	CAS	.
Donidalorsen sodium	Y30VEG5PH1	2304701-45-7

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]

Donidalorsen is under investigation in clinical trial NCT05392114 to assess the long-term safety and efficacy of donidalorsen in the prophylactic treatment of hereditary angioedema (HAE)

Donidalorsen is an antisense oligonucleotide designed to reduce the production of prekallikrein (PKK). PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of Hereditary angioedema (HAE).

https://ir.ionis.com/news-releases/news-release-details/dawnzeratm-donidalorsen-approved-us-first-and-only-rna-targeted

AWNZERA™ (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema

August 21, 2025

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– DAWNZERA demonstrated significant and sustained HAE attack rate reduction and long-term disease control –

– Offers longest dosing option for HAE, with dosing every 4 or 8 weeks –

– Compelling profile supported by recently published switch data –

– Ionis’ second independent launch in just nine months, with potential for two additional launches next year –

– Ionis to host webcast today at 12:15pm ET –

CARLSBAD, Calif.–(BUSINESS WIRE)–Aug. 21, 2025– Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that the U.S. Food and Drug Administration (FDA) has approved DAWNZERA™ (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is the first and only RNA-targeted medicine approved for HAE, designed to target plasma prekallikrein (PKK), a key protein that activates inflammatory mediators associated with acute attacks of HAE. DAWNZERA 80mg is self-administered via subcutaneous autoinjector once every four (Q4W) or eight weeks (Q8W).

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250818615141/en/

DAWNZERA (donidalorsen) logo

HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. HAE is estimated to affect approximately 7,000 people in the U.S.

“DAWNZERA represents a significant advance for people living with HAE who need improved treatment options. With strong and durable efficacy, convenient administration and the longest dosing option available, we believe DAWNZERA will be the prophylactic treatment of choice for many people living with HAE. Importantly, the recently published switch data empowers patients and physicians with a roadmap for switching to DAWNZERA from other prophylactic therapies,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “At Ionis, we are dedicated to turning groundbreaking science into life-changing medicines. With the early success of our first independent launch of TRYNGOLZA® for familial chylomicronemia syndrome (FCS), and now with DAWNZERA, our second independent medicine approved in less than nine months, we are proudly delivering on that vision. To the patients, families, advocacy partners and investigators who helped make this moment a reality, we express our deepest gratitude.”

The approval of DAWNZERA was based on positive results from the Phase 3 global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE study in patients with HAE. The study met its primary endpoint, with DAWNZERA Q4W significantly reducing monthly HAE attack rate by 81% compared to placebo over 24 weeks. Mean attack rate reduction increased to 87% when measured from the second dose, a key secondary endpoint. Additionally, DAWNZERA Q4W reduced moderate-to-severe HAE attacks by ~90% over 24 weeks when measured from the second dose.

These results are bolstered by the ongoing OASISplus open-label extension (OLE) study, in which DAWNZERA Q8W had a similar effect as Q4W over time. DAWNZERA demonstrated 94% total mean attack rate reduction from baseline across both dosing groups after one year in the OLE.

The OASISplus study also includes a switch cohort evaluating DAWNZERA Q4W in patients previously treated with lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks. Switching to DAWNZERA reduced mean HAE attack rate by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks observed during the switch. A total of 84% of patients surveyed preferred DAWNZERA over their prior prophylactic treatment, citing better disease control, less time to administer and less injection site pain or reactions.

Across clinical studies, DAWNZERA demonstrated a favorable safety and tolerability profile. The most common adverse reactions (incidence ≥ 5%) were injection site reactions, upper respiratory tract infection, urinary tract infection and abdominal discomfort.

“As the first FDA-approved RNA-targeted therapy for HAE, DAWNZERA represents a welcome advance in therapeutic options for preventing attacks. Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” said Anthony J. Castaldo, CEO & chairman of the board, U.S. Hereditary Angioedema Association (HAEA) and Hereditary Angioedema International (HAEi).

“People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful and dangerous breakthrough attacks even with current treatments. Durable efficacy is essential in maintaining long-term disease control,” said Marc Riedl, M.D., M.S., clinical director, U.S. HAEA Angioedema Center; University of California, San Diego; OASIS-HAE and OASISplus trial investigator. “DAWNZERA is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment.”

DAWNZERA will be available in the U.S. in the coming days.

Ionis is committed to helping people access the medicines they are prescribed and will offer a suite of services designed to meet the unique needs of the HAE community through Ionis Every Step™. As part of Ionis Every Step, patients and healthcare providers will have access to a wide range of support and resources including dedicated support from a Patient Education Manager, assistance with the insurance approval process, information on affordability programs, access to the DAWNZERA Direct digital companion and other ongoing services and resources to help patients stay on track. Visit DAWNZERA.com for more information.

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References

1.  “DAWNZERA (donidalorsen) injection, for subcutaneous use” (PDF). Highlights of Prescribing Information. Ionis Pharmaceuticals, Inc.
2.  “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.  “Donidalorsen: An Investigational RNA-targeted Medicine” (PDF). Ionis Pharmaceuticals, Inc.
4.  Farkas H, Balla Z (March 2024). “Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies”. Expert Opinion on Investigational Drugs. 33 (3): 191–200. doi:10.1080/13543784.2024.2320700. PMID 38366937.
5.  “Dawnzera: FDA-Approved Drugs”. U.S. Food and Drug Administration (FDA). Retrieved 22 August 2025.
6.  World Health Organization (2021). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 86”. WHO Drug Information. 35 (3). hdl:10665/346562.

Further reading

• Raja A, Shuja MH, Raja S, Qammar A, Kumar S, Khurram L, et al. (December 2024). “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. 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

Clinical data
Trade names	Dawnzera
Other names	ISIS 721744, ISIS-721744
AHFS/Drugs.com	Dawnzera
License data	US DailyMed: Donidalorsen
Routes of administration	Subcutaneous
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
CAS Number	2304692-48-42304701-45-7
DrugBank	DB18751DBSALT003520
UNII	ZD4D8M32TLY30VEG5PH1

• [1]. Fijen LM, Riedl MA, Bordone L, et al. Inhibition of Prekallikrein for Hereditary Angioedema. N Engl J Med. 2022;386(11):1026-1033.  [Content Brief][2]. Valerieva A, Longhurst HJ. Treatment of hereditary angioedema-single or multiple pathways to the rescue. Front Allergy. 2022;3:952233.  [Content Brief]

//////////Donidalorsen, FDA 2025, APPROVALS 2025, Dawnzera, ISIS-721744 FREE ACID, ISIS 721744