Olezarsen

Olezarsen

Olezarsen is an ASO directed inhibitor of Apolipoprotein C-III (apoC-III) mRNA, conjugated to a ligand containing three N-acetyl galactosamine (GalNAc) residues to enable delivery of the ASO to hepatocytes.

TRYNGOLZA contains olezarsen sodium as the active ingredient. Olezarsen sodium is a white to yellow solid and it is freely soluble in water and in phosphate buffer. The molecular formula of olezarsen sodium is C 296H 419N 71O 154P 20S 19Na 20and the molecular weight is 9124.48 daltons. The chemical name of olezarsen sodium is DNA, d(P-thio) ([2′- O-(2-methoxyethyl)] rA-[2′- O-(2-methoxyethyl)] rG-[2′- O-(2-methoxyethyl)] m5rC-[2′- O-(2-methoxyethyl)] m5rU-[2′- O-(2-methoxyethyl)] m5rU-m5C-T-T-G-T-m5C-m5C-A-G-m5C-[2′- O-(2-methoxyethyl)] m5rU-[2′- O-(2-methoxyethyl)] m5rU-[2′- O-(2-methoxyethyl)] m5rU-[2′- O-(2-methoxyethyl)] rA-[2′- O-(2-methoxyethyl)]m5rU), 5′-[26-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate], sodium salt (1:20).

Olezarsen

FDA APPROVED 12/19/2024, Tryngolza, To treat familial chylomicronemia syndrome
Drug Trials Snapshot

Synonyms

• AKCEA-APOCIII-LRX
• 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
• DNA, D(P-THIO)((2′-O-(2-METHOXYETHYL))RA-(2′-O-(2-METHOXYETHYL))RG-(2′-O-(2-METHOXYETHYL))M5RC-(2′-O-(2-METHOXYETHYL))M5RU-(2′-O-(2-METHOXYETHYL))M5RU-M5C-T-T-G-T-M5C-M5C-A-G-M5C-(2′-O-(2-METHOXYETHYL))M5RU-(2′-O-(2-METHOXYETHYL))M5RU-(2′-O-(2-METHOXYETH
• IONIS-APOCIII-LRX
• ISIS-APOCIII-LRX

External IDs 

• ISIS-678354

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]

PATENT

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US9127276	No	2015-09-08	2034-05-01
US9181549	No	2015-11-10	2034-05-01
US9593333	No	2014-02-14	2034-02-14
US9157082	No	2012-04-27	2032-04-27
US9163239	No	2014-05-01	2034-05-01

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

^ Jump up to:^{a b c d e f g} “Tryngolza- olezarsen sodium injection, solution”. DailyMed. 19 December 2024. Retrieved 25 January 2025.

1. ^ 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.
2. ^ Jump up to:^a b “Novel Drug Approvals for 2024”. U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 20 December 2024.
3. ^ 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.
4. ^ Jump up to:^a b 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.
5. ^ 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.
6. ^ “Olezarsen Orphan Drug Designations and Approvals”. U.S. Food and Drug Administration (FDA). Retrieved 20 December 2024.
7. ^ “EU/3/24/2973 – orphan designation for treatment of familial chylomicronaemia syndrome | European Medicines Agency (EMA)”. http://www.ema.europa.eu. 21 August 2024. Retrieved 22 February 2025.
8. ^ “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.
9. ^ 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

1. Tardif JC, Karwatowska-Prokopczuk E, Amour ES, Ballantyne CM, Shapiro MD, Moriarty PM, Baum SJ, Hurh E, Bartlett VJ, Kingsbury J, Figueroa AL, Alexander VJ, Tami J, Witztum JL, Geary RS, O’Dea LSL, Tsimikas S, Gaudet D: Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022 Apr 6;43(14):1401-1412. doi: 10.1093/eurheartj/ehab820. [Article]
2. Karwatowska-Prokopczuk E, Tardif JC, Gaudet D, Ballantyne CM, Shapiro MD, Moriarty PM, Baum SJ, Amour ES, Alexander VJ, Xia S, Otvos JD, Witztum JL, Tsimikas S: Effect of olezarsen targeting APOC-III on lipoprotein size and particle number measured by NMR in patients with hypertriglyceridemia. J Clin Lipidol. 2022 Sep-Oct;16(5):617-625. doi: 10.1016/j.jacl.2022.06.005. Epub 2022 Jun 23. [Article]
3. Hooper AJ, Bell DA, Burnett JR: Olezarsen, a liver-directed APOC3 ASO therapy for hypertriglyceridemia. Expert Opin Pharmacother. 2024 Oct;25(14):1861-1866. doi: 10.1080/14656566.2024.2408369. Epub 2024 Sep 26. [Article]
4. Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Murphy SA, Goodrich EL, Zhang S, Gaudet D, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS: Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk. N Engl J Med. 2024 May 16;390(19):1770-1780. doi: 10.1056/NEJMoa2402309. Epub 2024 Apr 7. [Article]
5. FDA News: FDA approves drug to reduce triglycerides in adult patients with familial chylomicronemia syndrome [Link]
6. FDA Approved Drug Products: TRYNGOLZA (olezarsen) injection, for subcutaneous use [Link]

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