Rare Daily Staff

Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals focused on developing and commercializing drugs to treat patients with serious cardiometabolic diseases caused by lipid disorders, initiated an exploratory mid-stage program of an experimental therapy to treat patients with rare hyperlipidemias, elevated levels of lipids and lipoprotein in the blood.

AKCEA-ANGPTL3-LRx is an experimental therapeutic designed to reduce the production of angiopoietin-like 3, or ANGPTL3, a key regulator of a number of lipid and metabolic pathways. The absence of ANGPTL3 has been shown to be cardioprotective and associated with reduced risk of insulin resistance and diabetes mellitus.

The mid-stage program includes three clinical studies in patients with one of three rare hyperlipidemias, including familial chylomicronemia syndrome, familial partial lipodystrophy, and homozygous familial hypercholesterolemia. The studies will determine the pharmacodynamics, pharmacokinetics, safety, and tolerability of AKCEA-ANGPTL3-LRx, and better determine the drug’s potential to treat these patient populations.

These rare conditions can lead to serious health consequences. In familial chylomicronemia syndrome, severe elevation of triglycerides results in a high risk of acute and chronic pancreatitis and other metabolic complications. Patients with homozygous familial hypercholesterolemia are subject to early cardiovascular disease and premature death due to high LDL cholesterol levels. Patients with familial partial lipodystrophy often have both high triglycerides and high LDL cholesterol levels, as well as other complications related to insulin resistance and fatty liver, which can lead to accelerated atherogenesis and liver failure.

In a Phase 1/2 clinical study in volunteers with elevated triglycerides, published in The New England Journal of Medicine, treatment with multiple doses of AKCEA-ANGPTL3-LRx resulted in dose-dependent reductions in ANGPTL3 protein of up to 85 percent after six weeks of treatment.

Treatment with AKCEA-ANGPTL3-LRx also resulted in substantial and dose-dependent reductions in triglycerides, LDL cholesterol, VLDL cholesterol, non-HDL cholesterol, apolipoprotein B and apolipoprotein C-III protein.

AKCEA-ANGPTL3-LRx was well tolerated in the study. No serious adverse events, including platelet count reductions and injection site reactions, were reported. Further, there were no discontinuations during the treatment period.

November 15, 2017

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