Pfizer and Ionis Pharmaceuticals have decided to discontinue the clinical development program for vupanorsen (PF-07285557), an investigational antisense therapy that was being evaluated for potential indications in cardiovascular risk reduction and severe hypertriglyceridemia.

The decision was made based on an analysis of data from the global multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b study ( Identifier: NCT04516291) evaluating vupanorsen in patients with dyslipidemia who were receiving a stable dose of statin.

The primary endpoint of the trial was the change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) at week 24.

Results showed that vupanorsen was associated with statistically significant reductions in non-HDL-C, triglycerides, and angiopoietin-like 3; however, the non-HDL-C and triglyceride reductions were not large enough to support continuation of the program.

Moreover, vupanorsen was associated with dose-dependent elevations in liver fat, alanine aminotransferase and aspartate aminotransferase.

“While this outcome is disappointing, the clinical and scientific knowledge derived from the vupanorsen program will hopefully contribute to a greater understanding of cardiovascular risk reduction and severe hypertriglyceridemia and the current gaps in treating these conditions,” said James Rusnak, MD, PhD, senior vice president and chief development officer, internal medicine and hospital, Pfizer.


Pfizer and Ionis announce discontinuation of vupanorsen clinical development program. News release. Ionis Pharmaceuticals, Inc. Accessed January 31, 2022.