Lipid-efficacy RCT · N Engl J Med 2024
Bridge-TIMI 73a trial
Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.
The bottom line
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.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Monthly subcutaneous olezarsen (50-mg or 80-mg cohort)
- Compared with
- Matching placebo
- People
- 154
- Who took part
- Adults with moderate hypertriglyceridemia (triglyceride level 150-499 mg/dL) and elevated cardiovascular risk, or severe hypertriglyceridemia (triglyceride level ≥500 mg/dL); median age 62 years, median triglyceride level 241.5 mg/dL; 24 sites in North America
- Design
- Phase 2b, randomized, controlled trial (1:1 to 50-mg or 80-mg cohort, then 3:1 olezarsen vs placebo within each cohort)
- Follow-up
- 6 months
- Main question
- Percent change in triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo
Main result
The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons).
Effect on LDL cholesterol
No significant change in the LDL cholesterol level
Other results
Each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, as compared with placebo
Safety
The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups.
In the trial's own words
“The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons).”
Quoted from the abstract of N Engl J Med 2024, checked word for word against PubMed. PubMed 38587249 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Olezarsen (Tryngolza) and volanesorsen
Common questions
What did the Bridge-TIMI 73a trial find?
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.
Who was in Bridge-TIMI 73a?
154 people. Adults with moderate hypertriglyceridemia (triglyceride level 150-499 mg/dL) and elevated cardiovascular risk, or severe hypertriglyceridemia (triglyceride level ≥500 mg/dL); median age 62 years, median triglyceride level 241.5 mg/dL; 24 sites in North America.
What was Bridge-TIMI 73a's main result?
The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons).
How much did LDL cholesterol change in Bridge-TIMI 73a?
No significant change in the LDL cholesterol level
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.
- Balance (2024)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.
- 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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