Vupanorsen is an investigational antisense therapy, discovered by Ionis Pharmaceuticals and co-developed by Ionis and its subsidiary Akcea Therapeutics
The entrance to Pfizer World Headquarters in Manhattan, New York. (Credit: Coolcaesar/Wikipedia.)
Pfizer has commenced a Phase 2b study of vupanorsen, in statin-treated patients with elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs).
The clinical trial, Targeting ANGPTL3 with an antisense oligonucleotide in adults with dyslipidemia (TRANSLATE-TIMI 70), is designed to assess different doses of vupanorsen to support the potential future development.
Vupanorsen is an investigational antisense therapy, discovered by Ionis Pharmaceuticals and co-developed by Ionis and its subsidiary Akcea Therapeutics.
In November 2019, Akcea and Ionis have reached an exclusive licensing agreement with Pfizer, for the development and regulatory activities and costs related to vupanorsen.
Under the terms of the licensing agreement, the initiation of the Phase 2b study is associated with a milestone payment of $75m from Pfizer.
Ionis global cardiovascular development vice president Sam Tsimikas said: “Results from the Phase 2a study recently presented at the ESC Congress and published in the European Heart Journal, showed that antisense-mediated reduction of ANGPTL3 has the potential to address unmet needs in patients with atherosclerotic cardiovascular diseases, and adds to the growing body of evidence supporting our LICA antisense technology.
“We look forward to seeing Pfizer advance the Phase 2b study and report results on this clinical programme.”
Vupanorsen was developed using LIgand Conjugated Antisense technology
Vupanorsen has been developed using Ionis’ advanced LIgand Conjugated Antisense (LICA) technology platform to inhibit the production of angiopoietin-like 3 (ANGPTL3) protein, which an important regulator of triglyceride and cholesterol metabolism in the liver.
In a previous Phase 1 study, treatment using vupanorsen resulted in a dose-dependent reduction in ANGPTL3, TG, LDL-C, non-HDL-C and total cholesterol with a favourable safety and tolerability profile.
The Phase 2a study showed that vupanorsen treatment has met the primary endpoint of a significant reduction in TG levels and multiple secondary endpoints, with a favourable safety and tolerability profile.
Pfizer has treated the first patient in the Phase 2b study, designed to assess the efficacy, safety, tolerability and pharmacokinetics of vupanorsen, and explore different doses and dose regimens compared to placebo.
The study will enrol a total of 260 participants, aged 40 years or above with elevated levels of non-HDL-C and triglycerides, and taking stable dose statin.
In the clinical trial, patients will receive either 80mg, 120mg or 160mg every four weeks, or 60mg, 80mg, 120mg or 160mg every two weeks via subcutaneous injection.
The primary endpoint of the study is per cent change from baseline in non-HDL-C at week 24.