Donidalorsen

Donidalorsen
Clinical data
Trade namesDawnzera
Other namesISIS 721744, ISIS-721744
AHFS/Drugs.comDawnzera
License data
Routes of
administration		Subcutaneous
ATC code
  • None
Legal status
Legal status
Identifiers
  • all-P-ambo-5'-O-(((6-(5-((tris(3-(6-(2-acetamido-2-deoxy-β-D-galactopyranosyloxy)hexylamino)-3-oxopropoxymethyl))methyl)amino-5-oxopentanamido)hexyl))phospho)-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methylcytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenosine
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC296H435N83O151P20S15
Molar mass8672.54 g·mol−1
  • COCCO[C@@H]1[C@H](OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2O)[C@@H](COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cnc4c(=O)[nH]c(N)nc43)O[C@@H]2COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(=O)(O)OCCCCCCNC(=O)CCCC(=O)NC(COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)(COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)O[C@H]1n1cc(C)c(N)nc1=O
  • InChI=1S/C296H435N83O151P20S15/c1-139-87-360(286(407)341-239(139)297)190-77-152(513-537(428,552)477-104-169-156(81-194(493-169)364-93-145(7)261(399)355-292(364)413)516-540(431,555)478-105-170-158(83-196(494-170)366-95-147(9)263(401)357-294(366)415)517-541(432,556)481-107-172-160(85-198(496-172)371-130-335-210-257(371)347-283(309)351-266(210)404)520-544(435,559)482-108-173-159(84-197(497-173)370-129-334-209-256(370)346-282(308)350-265(209)403)519-542(433,557)479-102-167-154(79-192(491-167)362-89-141(3)241(299)343-288(362)409)518-545(436,560)485-116-182-223(233(459-71-61-446-18)275(507-182)376-135-331-206-247(305)319-126-325-253(206)376)525-533(421,422)471-113-177-221(232(458-70-60-445-17)274(504-177)375-134-330-205-246(304)318-125-324-252(205)375)523-535(425,426)473-115-180-226(237(463-75-65-450-22)277(506-180)378-137-333-208-249(307)321-128-327-255(208)378)528-550(441,565)487-118-183-227(235(461-73-63-448-20)271(502-183)368-91-143(5)243(301)345-290(368)411)529-547(438,562)484-110-175-216(394)229(455-67-57-442-14)269(499-175)373-132-328-203-244(302)316-123-322-250(203)373)165(489-190)100-474-538(429,553)514-155-80-193(363-92-144(6)260(398)354-291(363)412)492-168(155)103-476-536(427,551)512-153-78-191(361-88-140(2)240(298)342-287(361)408)490-166(153)101-475-539(430,554)515-157-82-195(365-94-146(8)262(400)356-293(365)414)495-171(157)106-480-543(434,558)521-161-86-199(372-131-336-211-258(372)348-284(310)352-267(211)405)498-174(161)109-483-546(437,561)527-225-179(505-276(236(225)462-74-64-449-21)377-136-332-207-248(306)320-127-326-254(207)377)114-472-534(423,424)522-220-176(503-273(231(220)457-69-59-444-16)374-133-329-204-245(303)317-124-323-251(204)374)112-470-532(419,420)524-222-181(501-270(230(222)456-68-58-443-15)367-90-142(4)242(300)344-289(367)410)117-486-548(439,563)530-228-184(508-278(238(228)464-76-66-451-23)379-138-337-212-259(379)349-285(311)353-268(212)406)119-488-549(440,564)526-224-178(500-272(234(224)460-72-62-447-19)369-96-148(10)264(402)358-295(369)416)111-469-531(417,418)468-53-39-31-27-35-46-312-185(386)41-40-42-189(390)359-296(120-452-54-43-186(387)313-47-32-24-28-36-50-465-279-200(338-149(11)383)217(395)213(391)162(97-380)509-279,121-453-55-44-187(388)314-48-33-25-29-37-51-466-280-201(339-150(12)384)218(396)214(392)163(98-381)510-280)122-454-56-45-188(389)315-49-34-26-30-38-52-467-281-202(340-151(13)385)219(397)215(393)164(99-382)511-281/h87-96,123-138,152-184,190-202,213-238,269-281,380-382,391-397H,24-86,97-122H2,1-23H3,(H,312,386)(H,313,387)(H,314,388)(H,315,389)(H,338,383)(H,339,384)(H,340,385)(H,359,390)(H,417,418)(H,419,420)(H,421,422)(H,423,424)(H,425,426)(H,427,551)(H,428,552)(H,429,553)(H,430,554)(H,431,555)(H,432,556)(H,433,557)(H,434,558)(H,435,559)(H,436,560)(H,437,561)(H,438,562)(H,439,563)(H,440,564)(H,441,565)(H2,297,341,407)(H2,298,342,408)(H2,299,343,409)(H2,300,344,410)(H2,301,345,411)(H2,302,316,322)(H2,303,317,323)(H2,304,318,324)(H2,305,319,325)(H2,306,320,326)(H2,307,321,327)(H,354,398,412)(H,355,399,413)(H,356,400,414)(H,357,401,415)(H,358,402,416)(H3,308,346,350,403)(H3,309,347,351,404)(H3,310,348,352,405)(H3,311,349,353,406)/t152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162+,163+,164+,165+,166+,167+,168+,169+,170+,171+,172+,173+,174+,175+,176+,177+,178+,179+,180+,181+,182+,183+,184+,190+,191+,192+,193+,194+,195+,196+,197+,198+,199+,200+,201+,202+,213-,214-,215-,216+,217+,218+,219+,220+,221+,222+,223+,224+,225+,226+,227+,228+,229+,230+,231+,232+,233+,234+,235+,236+,237+,238+,269+,270+,271+,272+,273+,274+,275+,276+,277+,278+,279+,280+,281+,536?,537?,538?,539?,540?,541?,542?,543?,544?,545?,546?,547?,548?,549?,550?/m0/s1
  • Key:OHKXUCDSZDEIHM-ADAMUUMMSA-N

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]

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.[3][4]

Society and culture

Donidalorsen was approved for medical use in the United States in August 2025.[5]

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.[6] The applicant for this medicinal product is Otsuka Pharmaceutical Netherlands B.V.[6]

Names

Donidalorsen is the international nonproprietary name.[7]

Donidalorsen is sold under the brand name Dawnzera.[1]

References

  1. ^ a b c d e f "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. ^ a b "Dawnzera EPAR". European Medicines Agency (EMA). 14 November 2025. Retrieved 9 December 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ^ 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.
  • 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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