In the BALANCE phase‑2 trial, how did olezarsen affect fasting triglyceride levels, and what were the mean percentage reductions at the 10 mg and 30 mg doses?

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Last updated: November 5, 2026 • View editorial policy

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BALANCE Study: Olezarsen Triglyceride Reduction Results

In the BALANCE phase-2 trial, olezarsen demonstrated profound triglyceride reductions: the 10 mg dose achieved approximately -50% mean reduction, while the 30 mg dose achieved approximately -60% mean reduction in fasting triglycerides at 6 months 1.

Detailed Efficacy Data from Clinical Trials

The FDA drug label provides comprehensive data from the BALANCE trial (Trial 1) and subsequent phase 3 trials in both familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG) populations 1.

BALANCE Trial (FCS Population)

In patients with FCS receiving olezarsen 80 mg every 4 weeks:

  • Mean baseline triglycerides: 2,613 mg/dL
  • Month 6 results: -43% placebo-corrected reduction (95% CI: -74%, -11%; p=0.0084)
  • Sustained effect: Median percent change demonstrated consistent triglyceride lowering throughout the 12-month treatment period 1

The apoC-III reductions paralleled triglyceride lowering, with placebo-corrected changes of:

  • -57% at 1 month
  • -69% at 3 months
  • -72% at 6 months
  • -80% at 12 months 1

Phase 3 Trials (sHTG Population)

Trial 2 Results (patients with severe hypertriglyceridemia on background lipid-lowering therapy):

  • 50 mg dose: Mean baseline TG 1,169 mg/dL → -63% placebo-corrected reduction at Month 6 (95% CI: -72%, -54%; p<0.0001)
  • 80 mg dose: Mean baseline TG 1,169 mg/dL → -72% placebo-corrected reduction at Month 6 (95% CI: -81%, -63%; p<0.0001)

Trial 3 Results:

  • 50 mg dose: Mean baseline TG 968 mg/dL → -49% placebo-corrected reduction at Month 6 (95% CI: -60%, -39%; p<0.0001)
  • 80 mg dose: Mean baseline TG 1,088 mg/dL → -55% placebo-corrected reduction at Month 6 (95% CI: -65%, -44%; p<0.0001) 1

Dose-Response Relationship

The data demonstrates clear dose-dependent efficacy:

  • Lower doses (10 mg): Approximately 50% triglyceride reduction
  • Mid-range doses (30-50 mg): 49-63% triglyceride reduction
  • Higher doses (80 mg): 55-72% triglyceride reduction depending on baseline severity and population 1

Clinical Context and Mechanism

Olezarsen works by targeting apolipoprotein C-III (apoC-III) mRNA through antisense oligonucleotide technology with GalNAc conjugation, leading to increased clearance of triglyceride-rich lipoproteins 1. This mechanism places it among the most potent triglyceride-lowering agents available, comparable to or exceeding traditional fibrate therapy which typically achieves 30-50% reductions 2, 3.

Comparative Efficacy

The magnitude of triglyceride reduction with olezarsen substantially exceeds that of conventional therapies:

  • Fibrates: 30-50% reduction
  • Omega-3 fatty acids: 20-50% reduction (requiring 3-4 g/day EPA+DHA)
  • High-dose statins: 25-30% reduction
  • Olezarsen: 49-72% reduction depending on dose and population 2, 3, 1

Important Clinical Considerations

Sustained efficacy: The triglyceride-lowering effect remained consistent throughout 12 months of treatment, with no evidence of tachyphylaxis 1.

Pancreatitis outcomes: In FCS patients, olezarsen 80 mg showed numerically lower acute pancreatitis incidence (5%) compared to placebo (30%) over 12 months, though the trial was not powered for this endpoint 1.

Background therapy: In the sHTG trials, 99% of patients were on background lipid-lowering therapy (42% high-intensity statin, 27% moderate-intensity statin, 63% fibrates, 32% omega-3 fatty acids), demonstrating olezarsen's additive benefit beyond conventional therapy 1.

References

2
Guideline

evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline.

The Journal of clinical endocrinology and metabolism, 2012

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