Ionis Pharmaceuticals Inc. announced that Pfizer has provided an update on the Phase 2b study of vupanorsen, formerly IONIS-ANGPTL3-LRx. Vupanorsen is an investigational antisense therapy being developed for indications in cardiovascular (CV) risk reduction and severe hypertriglyceridemia (SHTG). In the dose-ranging study in subjects with elevated non-HDL-C and triglycerides (TG), the study met its primary endpoint, achieving a statistically significant reduction in non-HDL-C at all doses tested at 24 weeks, compared to placebo. In addition, subjects treated with vupanorsen achieved statistically significant reductions in TG and ANGPTL3 at all dose levels at 24 weeks, compared to placebo. The most common adverse events were injection site reactions, which occurred most often in the highest vupanorsen dose group. The most common laboratory abnormalities were increases in liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and were seen primarily at the higher doses. There were no Hy's Law cases in vupanorsen-treated subjects, and no meaningful changes in bilirubin. Certain doses of vupanorsen were associated with increases from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton density fat fraction at Week 24, compared to placebo. No subject had a confirmed platelet count abnormality or a confirmed reduction in the estimated glomerular filtration rate. There were no serious adverse events (SAEs) related to treatment. The incidence of SAEs was similar between active and placebo groups. The global multicenter, double-blind, placebo-controlled, dose-ranging Phase 2b study TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70) enrolled 286 participants (= 40 years old) with dyslipidemia, defined in this study as participants with elevated non-HDL-C (= 100 mg/dL) and TG (150-500 mg/dL), who are receiving a stable dose of a statin. Participants received either 80 mg, 120 mg or 160 mg every 4 weeks, or 60 mg, 80 mg, 120 mg or 160 mg every two weeks via subcutaneous injection. The study was designed to assess the efficacy, safety, tolerability and pharmacokinetics of vupanorsen, and the primary endpoint was percent change from baseline in non-HDL-C at week 24.