Olezarsen

Olezarsen

Clinical data
Trade names	Tryngolza
Other names	IONIS-APOCIII-LRX
License data	US  DailyMed:  Olezarsen
Routes of administration	Subcutaneous
Drug class	Antisense oligonucleotide
ATC code	None
Legal status
Legal status	US: ℞-only [1]
Identifiers
IUPAC name ALL-P-AMBO-5'-O-(((6-(5-((TRIS(3-(6-(2-ACETAMIDO-2-DEOXY-.BETA.-D-GALACTOPYRANOSYLOXY)HEXYLAMINO)-3-OXOPROPOXYMETHYL))METHYL)AMINO-5-OXOPENTANAMIDO)HEXYL))PHOSPHO)-2'-O-(2-METHOXYETHYL)-P-THIOADENYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-P-THIOGUANYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOCYTIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOURIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOURIDYLYL-(3'-O->5'-O)-2'-DEOXY-5-METHYL-P-THIOCYTIDYLYL-(3'-O->5'-O)-P-THIOTHYMIDYLYL-(3'-O->5'-O)-P-THIOTHYMIDYLYL-(3'-O->5'-O)-2'-DEOXY-P-THIOGUANYLYL-(3'-O->5'-O)-P-THIOTHYMIDYLYL-(3'-O->5'-O)-2'-DEOXY-5-METHYL-P-THIOCYTIDYLYL-(3'-O->5'-O)-2'-DEOXY-5-METHYL-P-THIOCYTIDYLYL-(3'-O->5'-O)-2'-DEOXY-P-THIOADENYLYL-(3'-O->5'-O)-2'-DEOXY-P-THIOGUANYLYL-(3'-O->5'-O)-2'-DEOXY-5-METHYL-P-THIOCYTIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOURIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOURIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYL-P-THIOURIDYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-P-THIOADENYLYL-(3'-O->5'-O)-2'-O-(2-METHOXYETHYL)-5-METHYLURIDINE
CAS Number	2097587-83-0 2298451-31-5
DrugBank	DB18728
UNII	S3RS2SA30L NSY2BY6PSB
KEGG	D13023

Olezarsen, sold under the brand name Tryngolza, is a medication used in the treatment of familial chylomicronemia syndrome. ^{[1] [2]} It is given by injection under the skin. ^[1]

Olezarsen was approved for medical use in the United States in December 2024. ^{[1] [3]} The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. ^[4]

Medical uses

Olezarsen is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome. ^[1]

Pharmacology

Olezarsen is an apolipoprotein C-III-directed antisense oligonucleotide. ^[1] By binding to apolipoprotein C-III mRNA, it causes its degradation, which in turn increases clearance of plasma triglycerides and very low-density lipoprotein (VLDL). ^[5]

Adverse effects

In a 66-patient trial, olezarsen was demonstrated to cause following side effects ^{[5] [6]} :

• injection site reactions
• hypersensitivity reactions (due to immunogenic potential of the medication)
• arthralgia
• thrombocytopenia
• hyperglycemia
• elevation of liver enzymes

History

The US Food and Drug Administration (FDA) granted the application of olezarsen orphan drug designation in February 2024. ^[7] In August 2024, European Medicines Agency also granted olezarsen this designation. ^[8]

Society and culture

Legal status

Olezarsen was approved for medical use in the United States in December 2024. ^{[3] [9]}

Names

Olezarsen is the international nonproprietary name. ^[10]

Olezarsen is sold under the brand name Tryngolza. ^[1]

References

1. "Tryngolza- olezarsen sodium injection, solution". DailyMed. 19 December 2024. Retrieved 25 January 2025.
2. Spagnuolo, Catherine M; Hegele, Robert A (2023). "Recent advances in treating hypertriglyceridemia in patients at high risk of cardiovascular disease with apolipoprotein C-III inhibitors". Expert Opinion on Pharmacotherapy. 24 (9): 1013–1020. doi: 10.1080/14656566.2023.2206015 . PMID   37114828.
3. "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 20 December 2024.
4. New Drug Therapy Approvals 2024 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2025. Archived from the original on 21 January 2025. Retrieved 21 January 2025.
5. Stroes, Erik S.G.; Alexander, Veronica J.; Karwatowska-Prokopczuk, Ewa; Hegele, Robert A.; Arca, Marcello; Ballantyne, Christie M.; et al. (16 May 2024). "Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome". New England Journal of Medicine. 390 (19): 1781–1792. doi:10.1056/NEJMoa2400201. ISSN   0028-4793.
6. Ionis Pharmaceuticals, Inc. (11 December 2024). A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) (Report). clinicaltrials.gov.
7. "Olezarsen Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). Retrieved 20 December 2024.
8. "EU/3/24/2973 - orphan designation for treatment of familial chylomicronaemia syndrome | European Medicines Agency (EMA)". www.ema.europa.eu. 21 August 2024. Retrieved 22 February 2025.
9. "Tryngolza (olezarsen) approved in U.S. as first-ever treatment for adults living with familial chylomicronemia syndrome as an adjunct to diet" (Press release). Ionis Pharmaceuticals. 19 December 2024. Retrieved 20 December 2024– via PR Newswire.
10. World Health Organization (2022). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87". WHO Drug Information. 36 (1). hdl: 10665/352794 .

Further reading

• Karwatowska-Prokopczuk, Ewa; Tardif, Jean-Claude; Gaudet, Daniel; Ballantyne, Christie M.; Shapiro, Michael D.; Moriarty, Patrick M.; et al. (2022). "Effect of olezarsen targeting APOC-III on lipoprotein size and particle number measured by NMR in patients with hypertriglyceridemia". Journal of Clinical Lipidology. 16 (5): 617–625. doi: 10.1016/j.jacl.2022.06.005 . PMID   35902351.
• Tardif, Jean-Claude; Karwatowska-Prokopczuk, Ewa; Amour, Eric St; Ballantyne, Christie M; Shapiro, Michael D; Moriarty, Patrick M; et al. (6 April 2022). "Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk". European Heart Journal. 43 (14): 1401–1412. doi: 10.1093/eurheartj/ehab820 . PMC   8986458 . PMID   35025993.

External links

• "Olezarsen (Code C180652)". NCI Thesaurus.
• Clinical trial number NCT04568434 for "A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS) (BALANCE)" at ClinicalTrials.gov