Drug Update · Cardiology

FDA Approves Olezarsen for Severe Hypertriglyceridemia: Reduces TG and Pancreatitis Risk

August 28, 2026

Indication (sHTG)

Reduce TG and the risk of acute pancreatitis in adults with TG greater than or equal to 500 mg/dL

Primary endpoint result (Trial 2, 50 mg)

-63% (placebo-corrected difference in percent change in fasting TG at Month 6; 95% CI: -72%, -54%; p <0.0001) [3]

Primary endpoint result (Trial 2, 80 mg)

-72% (placebo-corrected difference in percent change in fasting TG at Month 6; 95% CI: -81%, -63%; p <0.0001) [3]

Recommended dose (sHTG)

50 mg subcutaneously once monthly; may increase to 80 mg once monthly if additional TG reduction is indicated [3]

Clinical Perspective

This FDA action affects clinicians who manage adults with severe hypertriglyceridemia, including cardiologists, lipidologists, endocrinologists, and primary care physicians treating patients with fasting TG greater than or equal to 500 mg/dL ^[3]^[2]. The approval supports use of TRYNGOLZA as an adjunct to diet to reduce TG and the risk of acute pancreatitis in this population, with recommended dosing options for sHTG detailed in the prescribing information ^[3]. Key unanswered clinical questions include which patients on background fibrates or omega-3 fatty acids derive the largest pancreatitis-risk reduction with TRYNGOLZA and how to integrate TRYNGOLZA into existing algorithms for sHTG management?

Dr. Arjun Sharma, MBBS, MD (General Medicine), DM (Cardiology) · Cardiology

The FDA approved TRYNGOLZA (olezarsen) to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL) on June 24, 2026, as reflected in the prescribing information and FDA announcements ^[1]^[3]. Clinicians should consult current prescribing information for full dosing guidance. The approval cites randomized, double-blind, placebo-controlled trials showing clinically meaningful percent reductions in fasting TG at Month 6 versus placebo in adults with sHTG ^[3]^[2].

Clinical Context

Olezarsen (brand: TRYNGOLZA) is an apolipoprotein C-III (apoC-III)-directed antisense oligonucleotide (ASO) designed to reduce serum apoC-III protein and thereby lower plasma triglycerides and very low-density lipoprotein (VLDL) ^[3]. The FDA approved TRYNGOLZA as an adjunct to diet for adults with familial chylomicronemia syndrome (FCS) and separately to reduce TG and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL) ^[3]. Clinicians should consult current prescribing information for full dosing guidance. The approval was announced in FDA communications listing Tryngolza among notable approvals and identifying the indication to reduce pancreatitis risk in sHTG on June 24, 2026 ^[1]^[2]. The pivotal evidence includes randomized, placebo-controlled trials enrolling adults with sHTG on optimized background lipid-lowering therapy ^[3].

Key Findings

In Trial 2 (one of two randomized, double-blind, placebo-controlled trials in adults with sHTG), TRYNGOLZA 50 mg produced a placebo-corrected difference in percent change in fasting triglycerides from baseline to Month 6 of -63% versus placebo (95% CI: -72%, -54%; p <0.0001) ^[3].
Clinicians should consult current prescribing information for full dosing guidance.
In Trial 2, TRYNGOLZA 80 mg produced a placebo-corrected difference in percent change in fasting triglycerides from baseline to Month 6 of -72% versus placebo (95% CI: -81%, -63%; p <0.0001) ^[3].
Across pooled Trial 2 and Trial 3, TRYNGOLZA demonstrated statistically significant decreases in fasting TG at Month 6 and Month 12; baseline mean (SD) fasting TG was 1,116 (990) mg/dL with a median of 793 mg/dL (range 379 to 13,545 mg/dL) ^[3].
For the FCS indication (Trial 1, NCT04568434), the difference between TRYNGOLZA 80 mg and placebo in percent change in fasting TG from baseline to Month 6 was -43% (95% CI: -74%, -11%; p=0.0084) ^[3]^[2].

Safety & Tolerability

Hypersensitivity reactions (including symptoms of chest tightness and shortness of breath, redness of the skin, chills, and muscle pain and tenderness) have been reported with TRYNGOLZA ^[2]^[3].
Injection site reactions were reported as one of the most common adverse reactions ^[2]^[3].
Decreased platelet count was reported as a common adverse reaction ^[2]^[3].
Joint pain or stiffness (arthralgia) was reported as a common adverse reaction ^[2]^[3].

Study Design

TRYNGOLZA labeling summarizes three randomized, double-blind, placebo-controlled trials: Trial 1 (NCT04568434) in adults with genetically identified familial chylomicronemia syndrome and fasting TG ≥880 mg/dL, and Trial 2 (NCT05079919) and Trial 3 (NCT05552326) enrolling adults with severe hypertriglyceridemia (fasting TG ≥500 mg/dL) on optimized, stable background lipid-lowering therapy ^[3]^[2]. Clinicians should consult current prescribing information for full dosing guidance. In pooled Trial 2 and Trial 3, patients were randomized to TRYNGOLZA 50 mg (n=354), TRYNGOLZA 80 mg (n=351), or placebo (n=356) administered subcutaneously once every 4 weeks for a 53-week treatment period; the primary endpoint was percent change in fasting TG from baseline to Month 6 (average of Weeks 25 and 27) compared with placebo ^[3]. The FDA approval for the sHTG pancreatitis-risk indication was announced June 24, 2026 ^[1]^[3].

FAQ

What is TRYNGOLZA (olezarsen) approved for?

TRYNGOLZA (olezarsen) is approved as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) and to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL). The approval for the sHTG pancreatitis-risk claim was announced June 24, 2026. Clinicians should consult current prescribing information for full dosing guidance.

How does olezarsen work?

Olezarsen is an apoC-III-directed antisense oligonucleotide (ASO) conjugated to GalNAc that binds to apoC-III mRNA leading to mRNA degradation and reduced serum apoC-III protein. Reduction of apoC-III protein leads to increased clearance of plasma triglycerides and very low-density lipoprotein (VLDL), resulting in lower fasting triglyceride levels in treated patients.

What is the recommended dose of TRYNGOLZA for sHTG and FCS?

For adults with severe hypertriglyceridemia (sHTG), the recommended dosage of TRYNGOLZA is 50 mg injected subcutaneously once monthly; for patients with sHTG who tolerate 50 mg and need additional triglyceride reduction, the dosage may be increased to 80 mg injected subcutaneously once monthly. For adults with familial chylomicronemia syndrome (FCS), the recommended dosage is 80 mg injected subcutaneously once monthly. Clinicians should consult current prescribing information for full dosing guidance.

What are the most common side effects of TRYNGOLZA?

Reported adverse reactions include injection site reactions, decreased platelet count, and joint pain or stiffness (arthralgia). Hypersensitivity reactions have been reported and may include chest tightness, shortness of breath, redness of the skin, chills, and muscle pain and tenderness. Safety monitoring and patient counseling should follow the prescribing information.

FDA Approves Olezarsen for Severe Hypertriglyceridemia: Reduces TG and Pancreatitis Risk

Direct Clinical Takeaway & Evidence Summary

FDA Approves Olezarsen for Severe Hypertriglyceridemia: Reduces TG and Pancreatitis Risk

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Cardiology in your inbox.

Related Clinical Updates

FDA Approves Etripamil for PSVT: 64% 30‑min Conversion in RAPID

AZALEA–TIMI 71: Abelacimab Reduced Bleeding Risk (HR 0.38) vs Rivaroxaban in AF

FDA Approves Wegovy for CV Risk in Adults with Obesity: MACE 6.5% vs 8%

Verified HCP Portal