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Meta-Analysis
19 June 2026

Comparative efficacy and safety of olezarsen versus volanesorsen for familial chylomicronemia syndrome: a matching-adjusted indirect comparison

Authors: Handrean Soran, Asia Sikora Kessler https://orcid.org/0000-0001-9417-6637, Montserrat Vera-Llonch https://orcid.org/0009-0007-0669-1657, Veronica J Alexander https://orcid.org/0000-0003-3729-5749, Paul Serafini https://orcid.org/0009-0007-9773-5837, Divya Pushkarna https://orcid.org/0000-0002-6680-4074, Elisabete Rodrigues, … Show All … , Erik Stroes https://orcid.org/0009-0000-7584-7677, Ulrike Schatz https://orcid.org/0000-0001-8009-9482, Ursula Kassner https://orcid.org/0000-0002-4536-7063, Zalmai Hakimi https://orcid.org/0000-0001-5835-8599 [email protected], Aletta Falk, and Koo Wilson https://orcid.org/0000-0002-8732-8249Author Info & Affiliations
https://doi.org/10.57264/cer-2026-0069
PDFFormats

Abstract

Background: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by severe hypertriglyceridemia causing recurrent acute pancreatitis (AP). Since FCS is a genetic deficiency in functional lipoprotein lipase, conventional triglyceride-lowering therapies are ineffective in this metabolic disorder. Apolipoprotein C-III (apoC-III) inhibitors, including volanesorsen and olezarsen, have emerged as targeted treatments for FCS. Aim: To compare the efficacy and safety of olezarsen 80 mg every four weeks (Q4W) versus volanesorsen 300 mg weekly (QW) in patients with FCS using an anchored matching-adjusted indirect comparison. Materials & methods: Individual patient data from the Balance trial of olezarsen (n = 45) were weighted to match baseline characteristics reported in the APPROACH trial of volanesorsen (n = 66). Outcomes included percent change in fasting triglycerides (TG) and apoC-III at 26 and 52 weeks, and risks of AP events and adverse events at 52 weeks. Results: At 52 weeks, mean differences in fasting TG and apoC-III were -27.4% (95% CI: -69.4, 14.5) and -21.3% (95% CI: -61.9, 19.3). Relative risks of AP, treatment-emergent adverse events, and serious adverse events were 0.23 (95% CI: 0.01, 5.02), 0.87 (95% CI: 0.66, 1.13) and 0.50 (95% CI: 0.08, 3.26) at week 52. The rate ratio for AP events per patient-year was 0.06 (95% CI: 0.003, 1.41). No comparisons were statistically significant. Conclusion: In this matching-adjusted indirect comparison, no statistically significant differences in outcomes were observed between olezarsen and volanesorsen in patients with FCS. These findings provide important comparative context in a setting where head-to-head evidence is unavailable.

Plain language summary

What is this article about?

Familial chylomicronemia syndrome (FCS) is a rare inherited condition where the body cannot properly break down specific type of fats in the blood, called triglycerides. This leads to very high triglyceride levels and can cause repeated episodes of acute pancreatitis (AP) (a painful and serious inflammation of the pancreas). Conventional triglyceride-lowering therapies usually do not sufficiently reduce triglycerides for people with FCS, so newer drugs that target a protein called apolipoprotein C-III (apoC-III; like olezarsen and volanesorsen) have been approved to treat FCS. The study compared the newer treatment olezarsen (administered at 80 mg once per four weeks) with volanesorsen (administered at 300 mg once per week) to see how well they work and how safe they are for people with FCS.

How was the study was done?

Individual patient data from a clinical trial of olezarsen was adjusted to make the patient profile comparable to that of a clinical trial of volanesorsen (the comparator of interest) based on age, sex, race/ethnicity, body mass index, triglyceride levels and history of AP. Researchers then assessed how much olezarsen decreased triglyceride and apoC-III levels compared with volanesorsen, as well as how likely patients receiving olezarsen were to experience AP and adverse events compared with patients receiving volanesorsen.

What were the results?

After 1 year of treatment, patients who received olezarsen reduced their triglyceride and apoC-III levels by 27% more and 21% more, respectively, compared with those who received volanesorsen. They also were 77% less likely to experience AP and 13% less likely to experience an adverse event. However, because the olezarsen and volanesorsen studies were both small, these differences were not large enough to conclude that one drug is more effective or safe.

What do the results mean?

In this study, there was no evidence of differences in outcomes between olezarsen and volanesorsen in the treatment of patients with FCS. This is a first comparison of two drugs which have not been compared directly in a randomized controlled clinical trial.

Supplementary Material

File (supplementary data.docx)

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