A thyroid hormone analogue developed by Swedish company Karo Bio could significantly lower ‘bad’ cholesterol levels in patients already taking statins, and without any significant side-effects, the results of a Phase II trial suggest.

In the placebo-controlled, double-blind, multicentre study published in the New England Journal of Medicine, 189 patients with hypercholesterolaemia who were already taking simvastatin or atorvastatin were given either placebo or Karo Bio’s liver-selective thyroid hormone receptor antagonist eprotirome at doses of 25mcg, 50mcg or 100mcg daily for 12 weeks.

Adding placebo or eprotirome 25mcg, 50mcg or 100mcg to statin therapy reduced mean levels of serum LDL cholesterol from 141mg per decilitre to, respectively, 127mg, 113mg, 99mg or 94mg per decilitre, reported researchers from the US and Sweden. In percentage terms, the mean reductions from baseline were 7% for placebo, 22% for eprotirome 25mcg, 28% for eprotirome 50mcg and 32% for eprotirome 100mcg.

Placebo-adjusted reductions in serum LDL cholesterol were 15%, 20% and 26% respectively with eprotirome 25mcg, 50mcg and 100mcg respectively, Karo Bio noted. Similar reductions were seen in levels of serum apolipoprotein B (14%, 19% and 24%), triglycerides (20%, 20% and 37%) and Lp(a) lipoprotein (17%, 22% and 34%).

These benefits were achieved without any significant changes in body weight, serum markers of bone turnover, heart rate or blood pressure, Karo Bio said. No abnormal cardiac rhythm or electrocardiography changes were observed, nor any patterns of symptoms suggesting clinical thyrotoxicosis or hypothyroidism.

In contrast to the natural hormone triiodothyronine and thyroxine, eprotirome is mainly distributed in the liver, where it exerts its beneficial effects on LDL cholesterol and other atherogenic lipoproteins, Karo Bio pointed out.

The development of non-selective naturally occurring thyroid hormone metabolites and synthetic thyroid hormone receptor agonists has been hampered by thyroid hormone-related adverse effects on, for example, the heart or bone.

Jens Kristensen, vice president, clinical development and chief medical officer for Karo Bio, said the Phase II results indicated that eprotirome had the potential to be a useful drug in high-risk patients currently on statins but unable to reach their LDL cholesterol goals – an area of “high unmet medical need”.