Adding eprotirome to statin therapy further reduced serum LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in a phase II study.
Eprotirome, an investigational thyroid hormone analogue, also decreased levels of two other atherogenic lipids—triglycerides and Lp(a) lipoprotein—which are known to have a comparatively poor response to statins alone, said Dr. Paul W. Ladenson of Johns Hopkins University, Baltimore, and his associates.
The investigators conducted a double-blind trial in 189 patients already taking simvastatin or atorvastatin to determine whether adding eprotirome would decrease levels of atherogenic lipoproteins even further. These subjects continued to have a mean LDL cholesterol level of 116 mg/dL despite statin therapy.
The study subjects were randomly assigned to receive placebo or one of three doses of eprotirome—25, 50, or 100 mcg—in the form of enteric-coated tablets for 12 weeks. The study was sponsored by Karo Bio, maker of eprotirome.
A total of 168 subjects completed the trial.
Serum LDL cholesterol decreased 22% from baseline levels at the lowest dose of eprotirome, 28% at the intermediate dose, and 32% at the high dose, compared with a 7% decrease with placebo.
The proportion of subjects who had an LDL level of less than 100 mg/dL was 36% at the lowest dose of eprotirome, 50% at the intermediate dose, and 57% at the high dose, compared with 6% with placebo.
“Eprotirome was associated with larger decreases in levels of serum LDL cholesterol than would be expected with a doubling of the statin dose,” Dr. Ladenson and his colleagues said (N. Engl. J. Med. 2010;362:906-16).
The drug lowered serum levels of the atherogenic compounds apolipoprotein B, triglycerides, and Lp(a) lipoprotein. However, it also decreased serum levels of the favorable compounds HDL cholesterol and apolipoprotein A-I.
Dr. Ladenson reported that he received consulting fees from Karo Bio and Genzyme.