Karo Bio heart drug promising in Phase II, says company

A 12-week, placebo controlled, double blind, randomised Phase IIa study was designed to explore whether clinically relevant LDL-cholesterol lowering can be achieved without adversely affecting the heart, bone, muscle and thyroid function.

Karo Bio said that its drug, KB2115, induced a pronounced and statistically significant lowering of LDL-cholesterol (-23% and -29% at 100 microgram and 200 microgram daily dosing, respectively). An improved Apo B/Apo A-1 ratio (a risk factor which strongly correlates with myocardial infarction) was also observed. Triglycerides were significantly reduced; averaging 38% at the 200 microgram dose level and even more profoundly in subjects with elevated levels.

In addition, the independent risk factor lipoprotein, which correlates with the development of cardiovascular disease, was lowered by up to 45% at the highest dose. While HDL remained unchanged in this study, data from a previous clinical study suggests that KB2115 promotes reverse cholesterol transport.

Thyroid hormone homeostasis in extra-hepatic tissues was preserved, i.e. the levels of TSH and T3 were preserved at normal levels. T4 levels were moderately decreased, but remained within normal levels. The heart, bone metabolism, and muscle parameters were unchanged. Transient, dose dependent effects on liver enzymes were noted, but considered to be benign. There were no consecutive ALT elevations above 3-fold upper limit of normal and no concomitant increases in bilirubin levels.

Per Olof Wallstrom, president of Karo Bio, said: “This study shows that KB2115 is a promising new agent for dyslipidemia. We have in this study evaluated the safety and efficacy of KB2115 monotherapy in the higher dose interval, and will now continue to investigate the effects of lower doses of KB2115 given concomitantly with statins. We are very encouraged by these positive results with KB2115, and excited about the continuation of its development.”