AZD8233 is a novel, investigational ASO therapy designed to reduce blood cholesterol levels in patients with hypercholesterolemia (elevated LDL-C levels in the blood)
The Discovery Centre overhead view. (Credit: AstraZeneca)
AstraZeneca, together with its partner Ionis Pharmaceuticals, has unveiled positive results for AZD8233, an investigational antisense oligonucleotide therapy, from the Phase 2b ETESIAN trial.
The antisense drug, administered at 50mg dose strength, has met the primary endpoint of reduction in low-density lipoprotein cholesterol (LDL-C) levels by 73%, from baseline.
The study has also met the secondary endpoints including a significant reduction in proprotein convertase subtilisin/kexin type 9 levels by 89%, which was maintained through week 14.
AZD8233 is a novel, investigational ASO therapy designed to reduce blood cholesterol levels in patients with hypercholesterolemia, or elevated LDL-C levels in the blood.
The drug works by inhibiting PCSK9 expression to increase LDL receptor levels, which results in lower LDL-C levels, and cuts the risk of developing coronary heart disease.
AstraZeneca biopharmaceuticals R&D executive vice president Mene Pangalos said: “Today, we are pleased to announce that ETESIAN Phase 2b for AZD8233 demonstrated a clear dose-response for both PCSK9 and LDL-C levels.
“The results underscore AZD8233’s potential best-in-class efficacy profile, and support its further development as a next-generation PCSK9 inhibitor that is easily self-administered monthly.”
ETESIAN is a randomised, double-blind, placebo-controlled, dose-ranging Phase 2b study of AZD8233 in patients with hypercholesterolemia, on a background of high-dose statin.
The trial evaluated three, 15mg, 50mg, and 90mg dose levels of AZD8233, administered as a monthly subcutaneous injection for 12 weeks.
In the study, AZD8233 was generally well-tolerated and showed reductions in LDL-C and PCSK9 levels in all study arms, compared to placebo.
Furthermore, results from the Phase 2b SOLANO trial, which evaluates the safety, efficacy and tolerability of AZD8233 in patients with hypercholesterolemia, are expected later this year.
Ionis Pharmaceuticals CEO Brett Monia said: “The positive results of the ETESIAN study, along with the clinical studies to date, reinforces our confidence that ION449 (AZD8233) is a potential new treatment option that may be able to change the current standard of care for patients affected by hypercholesterolemia who have cardiovascular disease.”