AstraZeneca has initiated a Phase IIb clinical trial of investigational antisense medicine, ION449 (AZD8233), in patients with dyslipidemia.
Being developed by AstraZeneca as part of a partnership between Ionis Pharmaceuticals and the company, ION449 is a LIgand Conjugated Antisense (LICA) medicine.
It is designed to lower blood cholesterol levels by targeting proprotein convertase subtilisin/kexin type 9 (PCSK9).
PCSK9 is an enzyme that controls the number of low-density lipoprotein cholesterol (LDL-C) receptors on the surface of cells.
Ionis has received a milestone payment of $20m from AstraZeneca for the initiation of the trial.
The randomised, double-blind, placebo-controlled trial will enrol around 108 adults aged between 18 and 75 with LDL-C levels between 70 and 190 mg/dL and are receiving moderate or high-intensity statin therapy.
The therapy is as defined by the American College of Cardiology/American Heart Association (ACC /AHA) guidelines on blood cholesterol management.
The effect of different doses of ION449 on LDL-C versus placebo at week 12 in patients taking baseline statin therapy will be the trial’s primary objective.
It will also analyse three dose levels of ION449 compared to placebo, all administered once a month by subcutaneous injection.
Secondary endpoints of the study include safety and tolerability of the treatment.
According to data from Phase I study, single subcutaneous doses of ION449 showed dose-dependent mean reductions in circulating plasma PCSK9 and LDL-C levels of over 90% and up to 70%, respectively.
Participants of the trial had a baseline LDL-C between 100mg/dL and 190mg/dL without concomitant statin therapy.
Ionis Pharmaceuticals senior vice-president, clinical development and cardiovascular franchise leader Sotirios Tsimikas said: “Results from the Phase I study showed that ION449 potently reduces PCSK9 and LDL cholesterol.
“ION449 demonstrated best-in-class potential for PCSK9 inhibition and LDL-C reduction, supporting larger clinical trials that are now underway to further evaluate efficacy and safety.”