4.4 Article

APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia

Journal

JOURNAL OF CLINICAL LIPIDOLOGY
Volume 17, Issue 3, Pages 406-411

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2023.04.007

Keywords

ApoCIII; Steatosis; Magnetic resonance; Therapy; Antisense

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The inhibition of apoC-III has positive effects on hepatic fat fraction, which is beneficial for the treatment of hepatic steatosis in patients with severe hypertriglyceridemia.
ApoC-III inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. It is unknown whether targeting apoC-III affects hepatic steatosis in patients with hypertriglyceridemia. We studied the effect of volanesorsen, a potent antisense oligonucleotide targeting APOC3 mRNA, on hepatic fat fraction (HFF) assessed by MRI in patients with severe hypertriglyceridemia (SHTG, triglycerides >500 mg/dL), familial partial lipodystrophy (FPL, triglycerides >200 mg/dL) and familial chylomi-cronemia syndrome (FCS, triglycerides >750 mg/dL). The data were evaluated individually in COM-PASS (SHTG), APPROACH (FCS), and BROADEN (FPL) trials. The baseline absolute HFF were ele-vated in all three trials and ranged from 6.3-18.1%. In COMPASS, compared to placebo, volanesorsen significantly reduced the absolute HFF by-3.02% (95% CI, (-5.60,-0.60), p = 0.009) (placebo-adjusted % change from baseline-24.2%, p = 0.034) from baseline to 6 months. In APPROACH a non-significant absolute-1.0% (95% CI,-2.9, 0.0, p = 0.13) reduction in HFF was noted from baseline to 12 months (placebo-adjusted % change from baseline-37.1%, p = 0.20). In BROADEN volanesorsen significantly reduced the absolute HFF by-8.34% (95% CI,-13.01,-3.67, p = 0.001) from baseline to 12 months (placebo-adjusted % change from baseline-52.7%, p = 0.004). In all 3 trials individually, a strong in-verse correlation was present between the baseline HFF and the change in HFF in the volanesorsen groups, but not in the placebo groups. In conclusion, apoC-III inhibition with volanesorsen has favorable effects in HFF in patients with different etiologies of hypertriglyceridemia.& COPY; 2023 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

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