Eplontersen

Eplontersen, sold under the brand name Wainua, is a medication used for the treatment of transthyretin-mediated amyloidosis.^[3] It is a transthyretin-directed antisense oligonucleotide.^[3] It was developed to treat hereditary transthyretin amyloidosis by Ionis Pharmaceuticals and AstraZeneca.^[6][7][8][9]

Eplontersen

Clinical data
Trade names	Wainua
Other names	AKCEA-TTR-LRx
AHFS/Drugs.com	Eplontersen
License data	US DailyMed: Eplontersen
Routes of administration	Subcutaneous
ATC code	N07XX21 (WHO)
Legal status
Legal status	CA: ℞-only[1][2] US: ℞-only[3] EU: Rx-only[4][5]
Identifiers
CAS Number	1637600-16-8
DrugBank	DB16199
UNII	0GRZ0F5XJ6
KEGG	D12754
Chemical and physical data
Formula	C296H437N77O156P20S13
Molar mass	8606.39 g·mol−1
SMILES COCCO[C@@H]1[C@H](O)[C@@H](COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(N)nc3=O)O[C@@H]2COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(N)nc3=O)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cnc4c(N)ncnc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(N)ncnc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(N)ncnc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(=O)[nH]c(N)nc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(N)ncnc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cc(C)c(N)nc3=O)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(N)ncnc43)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(O)(=S)O[C@H]2C[C@H](n3cnc4c(=O)[nH]c(N)nc43)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cnc4c(=O)[nH]c(N)nc43)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(=O)(O)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(N)nc3=O)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)NCC(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)OCCC(=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 InChI=1S/C296H437N77O156P20S13/c1-140-89-354(284(402)336-240(140)297)193-79-155(511-538(429,551)479-109-173-161(84-198(493-173)367-133-326-207-246(303)316-128-321-251(207)367)517-543(434,556)478-108-172-158(82-196(491-172)357-96-147(8)260(394)349-291(357)409)514-540(431,553)483-113-177-164(88-202(497-177)371-137-331-212-256(371)342-282(308)345-266(212)400)519-545(436,558)482-111-175-162(85-199(495-175)368-134-327-208-247(304)317-129-322-252(208)368)518-544(435,557)481-112-176-163(86-200(496-176)369-135-328-209-248(305)318-130-323-253(209)369)520-546(437,559)485-121-186-226(235(458-74-64-446-21)276(507-186)372-138-329-210-249(306)319-131-324-254(210)372)526-535(424,425)472-118-181-223(233(456-72-62-444-19)272(501-181)364-99-150(11)263(397)352-294(364)412)523-536(426,427)474-120-184-228(237(460-76-66-448-23)273(503-184)360-92-143(4)243(300)339-287(360)405)528-549(440,562)487-123-187-229(239(462-78-68-450-25)274(505-187)361-93-144(5)244(301)340-288(361)406)529-547(438,560)484-114-178-217(388)230(453-69-59-441-16)268(498-178)358-90-141(2)241(298)337-285(358)403)169(488-193)105-477-542(433,555)516-160-83-197(366-132-325-206-245(302)315-127-320-250(206)366)494-174(160)110-480-539(430,552)513-157-81-195(356-95-146(7)259(393)348-290(356)408)489-170(157)106-475-537(428,550)512-156-80-194(355-94-145(6)258(392)347-289(355)407)490-171(156)107-476-541(432,554)515-159-87-201(370-136-330-211-255(370)341-281(307)344-265(211)399)492-168(159)104-469-531(416,417)524-224-182(506-277(236(224)459-75-65-447-22)373-139-332-213-257(373)343-283(309)346-267(213)401)119-473-533(420,421)522-222-179(499-271(232(222)455-71-61-443-18)363-98-149(10)262(396)351-293(363)411)116-470-532(418,419)521-221-180(500-270(231(221)454-70-60-442-17)362-97-148(9)261(395)350-292(362)410)117-471-534(422,423)525-225-185(504-269(234(225)457-73-63-445-20)359-91-142(3)242(299)338-286(359)404)122-486-548(439,561)527-227-183(502-275(238(227)461-77-67-449-24)365-100-151(12)264(398)353-295(365)413)115-468-530(414,415)467-55-41-33-29-37-48-310-188(380)43-42-44-189(381)314-124-296(466-58-47-192(384)313-51-36-28-32-40-54-465-280-205(335-154(15)379)220(391)216(387)167(103-376)510-280,125-451-56-45-190(382)311-49-34-26-30-38-52-463-278-203(333-152(13)377)218(389)214(385)165(101-374)508-278)126-452-57-46-191(383)312-50-35-27-31-39-53-464-279-204(334-153(14)378)219(390)215(386)166(102-375)509-279/h89-100,127-139,155-187,193-205,214-239,268-280,374-376,385-391H,26-88,101-126H2,1-25H3,(H,310,380)(H,311,382)(H,312,383)(H,313,384)(H,314,381)(H,333,377)(H,334,378)(H,335,379)(H,414,415)(H,416,417)(H,418,419)(H,420,421)(H,422,423)(H,424,425)(H,426,427)(H,428,550)(H,429,551)(H,430,552)(H,431,553)(H,432,554)(H,433,555)(H,434,556)(H,435,557)(H,436,558)(H,437,559)(H,438,560)(H,439,561)(H,440,562)(H2,297,336,402)(H2,298,337,403)(H2,299,338,404)(H2,300,339,405)(H2,301,340,406)(H2,302,315,320)(H2,303,316,321)(H2,304,317,322)(H2,305,318,323)(H2,306,319,324)(H,347,392,407)(H,348,393,408)(H,349,394,409)(H,350,395,410)(H,351,396,411)(H,352,397,412)(H,353,398,413)(H3,307,341,344,399)(H3,308,342,345,400)(H3,309,343,346,401)/t155-,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+,185+,186+,187+,193+,194+,195+,196+,197+,198+,199+,200+,201+,202+,203+,204+,205+,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+,239+,268+,269+,270+,271+,272+,273+,274+,275+,276+,277+,278+,279+,280+,537?,538?,539?,540?,541?,542?,543?,544?,545?,546?,547?,548?,549?/m0/s1 Key:SPMKIPFVYCMYNS-KCPXHCKUSA-N

Eplontersen was approved for medical use in the United States in December 2023 and in the UK in October 2024.^{[3][10][11][12][13]}

Medical uses

Eplontersen is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.^[3]

Side effects

The most common adverse reactions include decreased vitamin A and vomiting.^[3]

Society and culture

Legal status

In October 2024, 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 Wainzua, intended for the treatment of adults with hereditary transthyretin-mediated amyloidosis (ATTRv) and stage 1 or 2 polyneuropathy.^[4] The applicant for this medicinal product is AstraZeneca AB.^[4][14] Eplontersen was authorized for medical use in the European Union in March 2025.^[4][5]

Names

Eplontersen is the international nonproprietary name.^[15]