Olezarsen

Olezarsen is an ASO-GalNAc 3 conjugate that binds to apoC-III mRNA leading to mRNA degradation and resulting in a reduction of serum apoC-III protein. Reduction of apoC-III protein leads to increased clearance of plasma TG and VLDL.

• TRYNGOLZA is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an APOC-III -directed antisense oligonucleotide (ASO) indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).

• TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to olezarsen or any of the excipients in TRYNGOLZA. Hypersensitivity reactions, including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias, requiring medical treatment have occurred [see Warnings and Precautions (5.1) ] .contraindicated

The recommended dosage of TRYNGOLZA is 80 mg administered subcutaneously once monthly. ( 2.1 ) Administer TRYNGOLZA into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a healthcare provider or caregiver administers the injection. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of TRYNGOLZA is 80 mg administered subcutaneously once monthly [see Dosage and Administration (2.2) ] . 2.2 Administration Instructions Prior to initiation, train patients and/or caregivers on proper preparation and administration of TRYNGOLZA [see Instructions for Use ] . Remove the single-dose autoinjector from the refrigerator 30 minutes prior to the injection and allow to warm to room temperature. Do not use other warming methods. Inspect TRYNGOLZA visually for particulate matter prior to administration. The solution should be clear and colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed prior to administration. Maintain a low-fat diet (≤20g fat per day) in conjunction with TRYNGOLZA. Inject TRYNGOLZA subcutaneously into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a healthcare provider or caregiver administers the injection. Administer TRYNGOLZA as soon as possible after a missed dose. Resume dosing at monthly intervals from the date of the most recently administered dose.

Hypersensitivity reactions have been reported in patients treated with olezarsen. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. ( 5.1 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias) have been reported in patients treated with TRYNGOLZA [see Adverse Reactions (6.1) ] . Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions [ see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ionis Pharmaceuticals Inc. at toll free number 1-833-644-6647 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of TRYNGOLZA cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TRYNGOLZA was evaluated in 66 patients with FCS enrolled in Trial 1 (NCT #04568434) [see Clinical Studies (14) ] . In this trial, 43 patients received at least one dose of TRYNGOLZA, 50 mg (N=21) or 80 mg (N=22) and 23 patients received placebo. TRYNGOLZA 50 mg is not an approved dosing regimen for FCS [see Dosage and Administration (2.1) ]. Across treatment groups, the mean age was 45 years and 42% of patients were male. Eighty-five percent (85%) of patients were White, 9% were Asian and 6% were reported as other races; 11% identified as Hispanic or Latino ethnicity. Forty-three (43) patients were exposed to TRYNGOLZA for a median of 52 weeks; 22 patients were treated with TRYNGOLZA 80 mg every 4 weeks for a median of 52 weeks.

8.1 Pregnancy Risk Summary There are no available data on TRYNGOLZA use in pregnant women to inform drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Patients with FCS are at risk for pancreatitis during pregnancy because of defects in lipid metabolism and increased triglyceride levels (see Clinical Considerations ) . In animal reproduction studies conducted with the unconjugated antisense oligonucleotide (lacking GalNAc) in rabbits and mice, no adverse effects on development or pregnancy were observed at doses 21 times or 20 times, respectively, the maximum recommended clinical dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20% respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk During pregnancy, triglyceride levels increase during the third trimester of pregnancy. In patients with underlying defects in lipid metabolism, such as FCS, severe gestational hypertriglyceridemia may occur, increasing the risk of acute pancreatitis during pregnancy.

Metabolism

Olezarsen steady state mean (SD) maximum concentrations (C max ) is 883 (662) ng/mL and area under the curve (AUC τ ) is 7440 (3880) ng*h/mL at the approved recommended dosage in patients with FCS. Olezarsen C max and AUC increase dose-proportionally following single subcutaneous doses ranging from 10 to 120 mg (i.e., 0.13- to 1.5-times the approved recommended dose) in healthy volunteers.

• Dec 19, 2024NDANDA218614Ionis Pharms Inc

1. 1Blood Triglycerides Increased4210%
2. 2Injection Site Erythema379.0%
3. 3Injection Site Pain317.6%
4. 4Product Dose Omission Issue256.1%
5. 5Arthralgia204.9%
6. 6Off Label Use204.9%
7. 7Injection Site Swelling194.6%
8. 8Pancreatitis Acute184.4%
9. 9Pancreatitis174.2%
10. 10Nausea163.9%
11. 11Injection Site Discolouration133.2%
12. 12Abdominal Pain122.9%
13. 13Injection Site Bruising122.9%
14. 14Injection Site Pruritus122.9%
15. 15Injection Site Rash122.9%

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Olezarsen as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia
  Completed · Phase 2 · Interventional · 154 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05355402updated 2026-04-23
• A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
  Completed · Phase 3 · Interventional · 1,478 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05610280updated 2026-02-10
• A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
  Completed · Phase 3 · Interventional · 617 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05079919updated 2026-02-10
• A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
  Active not recruiting · Phase 3 · Interventional · 24 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05185843updated 2025-12-12
• A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
  Active not recruiting · Phase 3 · Interventional · 60 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05130450updated 2025-12-12
• CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)
  Active not recruiting · Phase 3 · Interventional · 885 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05681351updated 2025-12-01
• A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia
  Completed · Phase 3 · Interventional · 446 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05552326updated 2025-10-22
• A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
  Completed · Phase 3 · Interventional · 66 enrolled · Ionis Pharmaceuticals, Inc.
  NCT04568434updated 2025-03-06
• Olezarsen Early Access Program for Patients With Familial Chylomicronemia Syndrome (FCS)
  Approved for marketing · Expanded access · Ionis Pharmaceuticals, Inc.
  NCT06360237updated 2024-12-27
• A Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 104 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05579860updated 2024-05-10

Frequently asked questions

How does Olezarsen work?

Olezarsen is an ASO-GalNAc 3 conjugate that binds to apoC-III mRNA leading to mRNA degradation and resulting in a reduction of serum apoC-III protein. Reduction of apoC-III protein leads to increased clearance of plasma TG and VLDL.

What is Olezarsen used for?

According to FDA labeling, Olezarsen carries indications including: TRYNGOLZA is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an APOC-III -directed antisense oligonucleotide (ASO) indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Olezarsen?

Olezarsen is classified as Antisense Oligonucleotide, APOC-III-directed RNA Interaction, Increased Cholesterol Elimination, Increased RNA Degradation.

What are the brand names for Olezarsen?

Olezarsen is marketed under brand names including Tryngolza.

What are the contraindications for Olezarsen?

Olezarsen labeling lists contraindications including: TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to olezarsen or any of the excipients in TRYNGOLZA. Hypersensitivity reactions, including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias, requiring medical treatment have occurred [see Warnings and Precautions (5.1) ] .. Always consult the full prescribing information and a clinician.