Olezarsen

Last updated

Olezarsen
Olezarsen sodium.svg
Clinical data
Trade names Tryngolza
Other namesIONIS-APOCIII-LRX
AHFS/Drugs.com Monograph
MedlinePlus a625020
License data
Routes of
administration 		Subcutaneous
Drug class Antisense oligonucleotide
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)-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyluridine
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C296H439N71O154P20S19
Molar mass 8684.73 g·mol−1
  • COCCO[C@@H]1[C@H](O)[C@@H](COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cnc4c(N)ncnc43)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)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=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)(=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(=O)[nH]c(N)nc43)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](n3cc(C)c(N)nc3=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)(=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](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)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=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)(=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](n3cnc4c(N)ncnc43)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(=O)[nH]c1=O
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  • Key:OXKUXVOOWUAAFP-WSMKVKJMSA-N

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 is an apolipoprotein C-III-directed antisense oligonucleotide. [1] [3] Olezarsen is an antisense oligonucleotide which inhibits the formation of apolipoprotein C3 (apoC-III), a protein that regulates both triglyceride metabolism and liver clearance of chylomicrons and other triglyceride-rich lipoproteins. [4] By reducing serum apoC-III, olezarsen increases clearance of plasma triglycerides. [4]

Contents

The most common side effects include injection site reactions, low platelet counts, and joint pain. [3]

Olezarsen was approved for medical use in the United States in December 2024. [3] [5] The US Food and Drug Administration considers it to be a first-in-class medication. [6]

Medical uses

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

Adverse effects

The most common side effects include injection site reactions, low platelet counts, and joint pain. [3] There are some reports of allergic (hypersensitivity) reactions, including difficulty breathing, rash, facial swelling, hives, chills, and muscle aches. [3]

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). [7]

History

The US Food and Drug Administration (FDA) granted the application of olezarsen orphan drug designation in February 2024. [8] In August 2024, the European Medicines Agency granted olezarsen an orphan drug designation. [9]

The FDA approved olezarsen based on evidence from a clinical trial (trial 1; NCT04568434) of 66 participants with familial chylomicronemia syndrome. [3] The trial was conducted at 29 sites in 11 countries including Canada, France, Italy, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, the United Kingdom, and the United States. [3] Of the 66 participants, 19 participants were from trial sites in the United States. [3] The benefits and side effects of olezarsen for participants with familial chylomicronemia syndrome were evaluated in the same single clinical trial. [3] Additional trials in participants with hypertriglyceridemia were used to support the safety assessment. [3] The number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety. [3] Enrolled participants were already using other treatments to lower triglycerides, including a low-fat diet and medications (such as fenofibrates, omega-3 fatty acids, and statins). [3] Participants were randomly assigned to receive olezarsen or placebo every four weeks for one year. [3] Neither the participants nor the health care providers knew which treatment was being given. [3]

Society and culture

Olezarsen was approved for medical use in the United States in December 2024. [3] [5] [10]

In July 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 Tryngolza, intended for the treatment of adults with familial chylomicronemia syndrome. [4] The applicant for this medicinal product is Ionis Ireland Limited. [4]

Names

Olezarsen is the international nonproprietary name. [11]

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

References

  1. 1 2 3 4 5 6 7 "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. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Drug Trials Snapshot: Tryngolza". U.S. Food and Drug Administration. 19 December 2024. Retrieved 24 June 2025.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. 1 2 3 4 "Tryngolza EPAR". European Medicines Agency (EMA). 25 July 2025. Retrieved 28 July 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. 1 2 "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 20 December 2024.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ "Olezarsen Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). Archived from the original on 27 December 2024. Retrieved 20 December 2024.
  9. ↑ "EU/3/24/2973 - orphan designation for treatment of familial chylomicronaemia syndrome". European Medicines Agency (EMA). 21 August 2024. Retrieved 22 February 2025.
  10. ↑ "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.
  11. ↑ World Health Organization (2022). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87". WHO Drug Information. 36 (1). hdl: 10665/352794 .

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