Ionis Pharmaceuticals and Pfizer have reported that their experimental antisense therapy, vupanorsen, met the primary goal of the Phase IIb TRANSLATE-TIMI 70 clinical trial to treat dyslipidemia.
Previously called IONIS-ANGPTL3-L, vupanorsen was discovered by Ionis and subsequently licensed to Pfizer under a global exclusive agreement in November 2019.
It is being developed for indications in cardiovascular risk reduction, as well as severe hypertriglyceridemia.
The international, double-blind, placebo-controlled, multicentre, dose-ranging trial analysed the safety, efficacy, tolerability and pharmacokinetics of vupanorsen in 286 subjects aged 40 years and above with dyslipidemia.
In the trial, dyslipidemia was described as patients with high non-HDL-C ≥ 100mg/dL and triglycerides (TG) ranging between 150mg/dL and 500mg/dL and receiving a statin dose.
Subjects were given either 80mg, 120mg or 160mg subcutaneous doses of vupanorsen every four weeks, or 60mg, 80mg, 120mg or 160mg every two weeks.
The percentage difference from baseline in non-HDL-C at week 24 was the trial’s primary goal.
Findings showed that treatment with vupanorsen offered a statistically significant decline in non-HDL-C at all doses tested at 24 weeks versus placebo, meeting the primary goal.
Furthermore, participants in the vupanorsen arm attained a statistically significant decline in TG, as well as angiopoietin-like-3 (ANGPTL3) at all tested doses at 24 weeks as against placebo.
Injection site reactions were the most common side effects observed in the trial, occurring most frequently in the highest vupanorsen dosage arm.
No serious adverse events (SAEs) linked to the antisense therapy were reported with the occurrence of SAEs to be similar between active and placebo arms.
Ionis Pharmaceuticals global cardiovascular development vice-president and cardiovascular franchise lead Sotirios Sam Tsimikas said: “We were pleased to see statistically significant reductions in the primary endpoint, non-HDL-cholesterol, and in the secondary endpoint of triglycerides at all doses tested.
“The topline results of the Phase IIb study also showed that vupanorsen dose-dependently lowered its target, angiopoietin-like 3.”
Earlier this month, Ionis started the Phase III CORE trial of its antisense medicine, olezarsen, in severe hypertriglyceridemia patients.