Pfizer, Ionis Pharma discontinue Vupanorsen Clinical Development Program

Pfizer made this decision after a thorough review of data from the global Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, 8-arm parallel-group study of vupanorsen in statin-treated participants with dyslipidemia — also known as TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70).

As previously announced, the study met its primary endpoint, achieving a statistically significant reduction in non-high density lipoprotein cholesterol (non-HDL-C) — as well as statistically significant reductions in triglycerides (TG) and angiopoietin-like 3 (ANGPTL3). However, the magnitude of non-HDL-C and TG reduction observed did not support continuation of the clinical development program for CV risk reduction or SHTG. Vupanorsen was also associated with dose-dependent increases in liver fat, and higher doses were associated with elevations in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Pfizer will return development rights to vupanorsen to Ionis, from which it licensed the investigational therapy in a worldwide exclusive agreement in November 2019.

"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, M.D., Ph.D., Senior Vice President and Chief Development Officer, Internal Medicine and Hospital, Pfizer. "Pfizer remains dedicated to research and development in the cardiovascular category and helping to address the unmet medical needs of patients with cardiovascular diseases. We are grateful to the patients, investigators and support staff who have participated in this important research program."

"Although this is not the outcome we would have liked, we are grateful for this collaboration with Pfizer, whose leadership in the development of vupanorsen has been instrumental in gaining important insights and learnings that will help us continue to deliver potentially life-transforming treatments for people impacted by cardiovascular disease," said Richard S. Geary, Ph.D., Executive Vice President and Chief Development Officer at Ionis.