Vupanorsen significantly reduced non-HDL-cholesterol and triglyceride levels at all doses studied and lowered additional lipid parameters at some doses, though with a modest effect on ApoB, according to data presented from the TRANSLATE-TIMI 70 study in adults with dyslipidaemia.1,2 However, the more frequent liver enzyme elevations and dose-related increases in hepatic fat fraction compared to placebo have resulted in the discontinuation of the drug’s development. ALT or AST >3xULN occurred in 0-9% of patients on vupanorsen Q4W regimens and 2-39% of those on Q2W regimens, compared with 0% in placebo groups. The least-squares mean relative change at week 24 compared with baseline in the hepatic fat fraction (measured by MRI) was 1.13-1.24 in vupanorsen Q4W regimens and 1.05-1.76 with Q2W regimens, compared to 0.99 with placebo.
Reference
- Bergmark B, Marston N, Bramson C et al. Effect Of Vupanorsen On Non-high-density Lipoprotein Cholesterol Levels In Statin-treated Patients With Elevated Cholesterol – TRANSLATE-TIMI 70. Presented at ACC.22, April 2-4 2022, Washington DC, USA, Late Breaker
- Bergmark BA, Marston NA, Bramson CR et al. Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 703. Circulation April 2022 online