Vupanorsen, an Investigational Antisense Oligonucleotide Targeting ANGPTL3, Meets Primary and Key Secondary Endpoints in Phase 2b Trial for Severe Hypertriglyceridemia

On November 24, 2021, Ionis Pharmaceuticals announced that vupanorsen, jointly developed with Pfizer, achieved the primary and key secondary endpoints in a Phase 2b clinical trial. Vupanorsen is an investigational antisense oligonucleotide therapy targeting ANGPTL3, aimed at reducing cardiovascular (CV) risk and treating severe hypertriglyceridemia. At 24 weeks, in subjects with elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TG), the drug significantly reduced non-HDL-C levels across all doses compared to placebo.

Vupanorsen Utilizes Ionis' Ligand-Conjugated Antisense (LICA) Technology to Target and Reduce Levels of the Key Regulator ANGPTL3 Protein in the Liver. ANGPTL3 is a Genetically Validated Target in Humans, Playing a Crucial Role in Regulating Triglycerides and Low-Density Lipoprotein Cholesterol (LDL-C).

In a Phase 2a trial, vupanorsen significantly reduced triglyceride levels in patients with hyperlipidemia, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Patients receiving vupanorsen at a dose of 80 mg (once every four weeks) showed an average reduction of 44% in fasting triglyceride levels compared to placebo (p<0.0001).

This multicenter, double-blind, placebo-controlled Phase 2b trial enrolled 286 subjects (≥40 years) with dyslipidemia, defined as elevated non-HDL-C (≥100 mg/dL) and TG (150-500 mg/dL), who were on a stable dose of statin therapy. In addition to achieving the primary endpoint, the trial also met key secondary endpoints, with statistically significant reductions in triglycerides and ANGPTL3 protein levels observed across all dose groups.

In terms of safety, the most common adverse events in the trial were injection site reactions, most frequently occurring in the highest dose group. No serious adverse events related to treatment occurred.

References:

[1] Ionis announces that Pfizer reports topline results from Phase 2b clinical study of vupanorsen. Retrieved November 24, 2021, from https://ir.ionispharma.com/news-releases/news-release-details/ionis-announces-pfizer-reports-topline-results-phase-2b-clinical

(Original text has been abridged)

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