Zilucoplan

Zilucoplan, sold under the brand name Zilbrysq, is a medication used for the treatment of generalized myasthenia gravis.^[5][8][9] It is a complement inhibitor that is injected subcutaneously (under the skin).^[5]

Zilucoplan

Clinical data
Trade names	Zilbrysq
Other names	RA101495
AHFS/Drugs.com	Monograph
MedlinePlus	a624002
License data	US DailyMed: Zilucoplan
Pregnancy category	AU: D[1]
Routes of administration	Subcutaneous
Drug class	Complement inhibitor
ATC code	L04AJ06 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[2][3][1] CA: ℞-only[4] US: ℞-only[5] EU: Rx-only[6][7]
Identifiers
IUPAC name (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,14S,22S)-22-acetamido-11-benzyl-8-(3-carbamimidamidopropyl)-5-(2-carboxyethyl)-3,6,9,12,16,23-hexaoxo-2-propan-2-yl-1,4,7,10,13,17-hexazacyclotricosane-14-carbonyl]-methylamino]-3-carboxypropanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-cyclohexylacetyl]amino]-6-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(4S)-4-carboxy-4-(hexadecanoylamino)butanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]hexanoic acid
CAS Number	1841136-73-9
PubChem CID	133083018
DrugBank	DB15636
ChemSpider	71115966
UNII	YG391PK0CC
KEGG	D12357
ChEBI	CHEBI:229659
Chemical and physical data
Formula	C172H278N24O55
Molar mass	3562.229 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC1=CNC2=NC=CC=C12)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)N(C)C(=O)[C@@H]1CC(=O)NCCCC[C@H](NC(C)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N1)C(C)(C)C)C1CCCCC1)C(O)=O)C(O)=O
InChI InChI=1S/C172H278N24O55/c1-9-10-11-12-13-14-15-16-17-18-19-20-27-44-146(202)182-136(170(226)227)53-56-144(200)177-64-67-229-69-71-231-73-75-233-77-79-235-81-83-237-85-87-239-89-91-241-93-95-243-97-99-245-101-103-247-105-107-249-109-111-251-113-112-250-110-108-248-106-104-246-102-100-244-98-96-242-94-92-240-90-88-238-86-84-236-82-80-234-78-76-232-74-72-230-70-68-228-66-59-145(201)175-60-31-29-41-135(169(224)225)186-165(220)152(126-37-25-22-26-38-126)193-162(217)142-43-34-65-196(142)168(223)140(116-125-47-51-129(199)52-48-125)190-157(212)133(54-57-148(204)205)184-161(216)139(117-127-120-180-154-130(127)39-32-62-178-154)188-159(214)138(115-124-45-49-128(198)50-46-124)189-166(221)153(172(5,6)7)194-163(218)143(119-150(208)209)195(8)167(222)141-118-147(203)176-61-30-28-40-131(181-122(4)197)158(213)192-151(121(2)3)164(219)185-134(55-58-149(206)207)156(211)183-132(42-33-63-179-171(173)174)155(210)187-137(160(215)191-141)114-123-35-23-21-24-36-123/h21,23-24,32,35-36,39,45-52,62,120-121,126,131-143,151-153,198-199H,9-20,22,25-31,33-34,37-38,40-44,53-61,63-119H2,1-8H3,(H,175,201)(H,176,203)(H,177,200)(H,178,180)(H,181,197)(H,182,202)(H,183,211)(H,184,216)(H,185,219)(H,186,220)(H,187,210)(H,188,214)(H,189,221)(H,190,212)(H,191,215)(H,192,213)(H,193,217)(H,194,218)(H,204,205)(H,206,207)(H,208,209)(H,224,225)(H,226,227)(H4,173,174,179)/t131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,151-,152-,153+/m0/s1 Key:JDXCOXKBIGBZSK-PSNKNOTQSA-N

Zilucoplan is a cyclic peptide that binds to the protein complement component 5 (C5) and inhibits its cleavage into C5a and C5b.^[10]

Zilucoplan was approved for medical use in the United States in October 2023,^[5][11] and in the European Union in December 2023.^[6]

Medical uses

Zilucoplan is indicated for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive.^[5]

Society and culture

Legal status

In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zilbrysq, intended for the treatment of myasthenia gravis.^[12] The applicant for this medicinal product is UCB Pharma S.A.^[12] Zilucoplan was approved for medical use in the Europea Union in December 2023.^[6]

Zilucoplan was granted orphan drug designation by the US Food and Drug Administration (FDA) in August 2019,^[13] and by the EMA in July 2022.^[14]

Brand names

Zilucoplan is the international nonproprietary name.^[15]

Zilucoplan is sold under the brand name Zilbrysq.^[6]

References

1. "Zilbrysq (zilucoplan)". Therapeutic Goods Administration (TGA). 24 September 2024. Retrieved 12 October 2024.
2. "Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024". Federal Register of Legislation. 30 May 2024. Retrieved 10 June 2024.
3. "Zilbrysq (UCB Australia Pty Ltd T/A UCB Pharma Division of UCB Australia)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
4. "Notice: Multiple additions to the Prescription Drug List (PDL) [2024-08-13]". Health Canada. 13 August 2024. Retrieved 15 August 2024.
5. "Zilbrysq- zilucoplan injection, solution". DailyMed. 19 July 2024. Retrieved 15 September 2024.
6. "Zilbrysq EPAR". European Medicines Agency. 1 December 2023. Retrieved 11 December 2023.
7. "Zilbrysq Product information". Union Register of medicinal products. 4 December 2023. Archived from the original on 11 December 2023. Retrieved 11 December 2023.
8. Howard JF, Kaminski HJ, Nowak RJ, Wolfe GI, Benatar MG, Ricardo A, et al. (April 2018). "RA101495, a subcutaneously administered peptide inhibitor of complement component 5 (C5) for the treatment of generalized myasthenia gravis (gMG): Phase 1 results and phase 2 design (S31. 006)". Neurology. 90 (15 Supplement). doi:10.1212/WNL.90.15_supplement.S31.006. S2CID 56969245. Archived from the original on 22 February 2022. Retrieved 24 June 2021.
9. Howard JF, Vissing J, Gilhus NE, Leite MI, Utsugisawa K, Duda PW, et al. (May 2021). "Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody-Positive Generalized Myasthenia Gravis". Expert Opinion on Investigational Drugs. 30 (5): 483–493. doi:10.1080/13543784.2021.1897567. hdl:11250/2770699. PMID 33792453. S2CID 232482753.
10. Ricardo A, Arata M, DeMarco S, Dhamnaskar K, Hammer R, Fridkis-Hareli M, et al. (2015). "Preclinical Evaluation of RA101495, a Potent Cyclic Peptide Inhibitor of C5 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria". Blood. 126 (23): 939. doi:10.1182/blood.V126.23.939.939.
11. "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 22 December 2023. Retrieved 27 December 2023.
12. "Zilbrysq: Pending EC decision". European Medicines Agency. 15 September 2023. Archived from the original on 26 September 2023. Retrieved 24 September 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
13. "Zilucoplan Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). Archived from the original on 17 October 2023. Retrieved 19 October 2023.
14. "EU/3/22/2650: Orphan designation for the treatment of myasthenia gravis". European Medicines Agency. 15 September 2023. Archived from the original on 29 January 2023. Retrieved 24 September 2023.
15. World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl:10665/330907.

External links

• Clinical trial number NCT04115293 for "Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE)" at ClinicalTrials.gov