Lipid-efficacy RCT · N Engl J Med 2024
Balance trial
Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome.
The bottom line
In patients with familial chylomicronemia syndrome, olezarsen 80 mg significantly lowered triglycerides and markedly reduced acute pancreatitis episodes compared with placebo, with the 50-mg dose not reaching significance for the triglyceride endpoint.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Olezarsen 80 mg or 50 mg subcutaneously every 4 weeks for 49 weeks
- Compared with
- Placebo
- People
- 66
- Who took part
- Patients with genetically identified familial chylomicronemia syndrome; baseline mean triglyceride 2630±1315 mg/dl; 71% had history of acute pancreatitis within previous 10 years
- Design
- phase 3, double-blind, placebo-controlled trial
- Follow-up
- 49 weeks treatment; assessed through 53 weeks
- Main question
- Percent change in fasting triglyceride level from baseline to 6 months, 80-mg olezarsen vs placebo (and, if significant, 50-mg olezarsen vs placebo)
Main result
Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% CI, -69.1 to -17.9; P<0.001) but not with the 50-mg dose (-22.4 percentage points; 95% CI, -47.2 to 2.5; P = 0.08)
Effect on LDL cholesterol
Not reported (triglyceride-focused trial); apolipoprotein C-III level change: -73.7 percentage points (95% CI, -94.6 to -52.8) for 80-mg vs placebo and -65.5 percentage points (95% CI, -82.6 to -48.3) for 50-mg vs placebo
Other results
By 53 weeks, 11 episodes of acute pancreatitis had occurred in the placebo group, and 1 episode had occurred in each olezarsen group (rate ratio [pooled olezarsen groups vs. placebo], 0.12; 95% CI, 0.02 to 0.66)
Safety
Adverse events of moderate severity that were considered by a trial investigator at the site to be related to the trial drug or placebo occurred in 4 patients in the 80-mg olezarsen group
In the trial's own words
“Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% confidence interval [CI], -69.1 to -17.9; P<0.001) but not with the 50-mg dose (-22.4 percentage points; 95% CI, -47.2 to 2.5; P = 0.08).”
Quoted from the abstract of N Engl J Med 2024, checked word for word against PubMed. PubMed 38587247 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Olezarsen (Tryngolza) and volanesorsen
Common questions
What did the Balance trial find?
In patients with familial chylomicronemia syndrome, olezarsen 80 mg significantly lowered triglycerides and markedly reduced acute pancreatitis episodes compared with placebo, with the 50-mg dose not reaching significance for the triglyceride endpoint.
Who was in Balance?
66 people. Patients with genetically identified familial chylomicronemia syndrome; baseline mean triglyceride 2630±1315 mg/dl; 71% had history of acute pancreatitis within previous 10 years.
What was Balance's main result?
Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% CI, -69.1 to -17.9; P<0.001) but not with the 50-mg dose (-22.4 percentage points; 95% CI, -47.2 to 2.5; P = 0.08)
How much did LDL cholesterol change in Balance?
Not reported (triglyceride-focused trial); apolipoprotein C-III level change: -73.7 percentage points (95% CI, -94.6 to -52.8) for 80-mg vs placebo and -65.5 percentage points (95% CI, -82.6 to -48.3) for 50-mg vs placebo
Related trials
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
- Bridge-TIMI 73a (2024)In patients with moderate-to-severe hypertriglyceridemia and elevated cardiovascular risk, monthly olezarsen substantially lowered triglycerides, APOC3, apolipoprotein B, and non-HDL cholesterol compared with placebo, without major safety concerns.
- SHASTA-2 (2024)Plozasiran markedly and durably lowered triglycerides (with most patients falling below the acute pancreatitis risk threshold) and APOC3 in severe hypertriglyceridemia, with a favorable safety profile, though it raised LDL-C without increasing ApoB and its effect on clinical complications remains unproven.
- CTX310 phase 1 (2025)A single dose of the CRISPR-Cas9 gene-editing therapy CTX310 was generally well tolerated and produced dose-dependent reductions in ANGPTL3 levels, supporting further clinical development for dyslipidemia.
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