A selective thyroid hormone receptor modulator for treatment of dyslipidemia

MARKET AND MEDICAL NEED
Dyslipidemia is a major risk factor for cardiovascular disease and one of the most prevalent conditions in the western world. The WHO estimates that, globally, dyslipidemia contributes to more than half of all ischemic heart disease cases and more than 4 million deaths per year.

Despite the success of statins, it is estimated that only half of those patients recieving statins reach recommended lipid treatment goals.

In a significant majority of the high risk patients, existing agents, even at maximal doses, do not achieve the recommended lipid goal levels.

It is estimated that 5-10 % of the patients cannot be treated with statins, due to side effects or lack of response

PRODUCT PROFILE
In a first phase II monotherapy study protirome induced a pronounced and statistically significant lowering of LDL-cholesterol in the range of 25-30 % at doses of 100 and 200 microgram daily.An improved Apo B/Apo A-1 ratio (a risk factor which strongly correlates with myocardial infarction) was also observed. Triglycerides and lipoprotein(a) were also significantly reduced. TSH and T3 were preserved at normal levels and heart, bone, and muscle parameters were unchanged. As for most cholesterol lowering drugs, a benign and transient elevation of liver transaminases was observed but there were no signs of liver toxicity.

In a second phase IIb study in 189 patients the effect of eprotirome as add on to statin treatment has been evaluated. The results show that eprotirome, in a dose dependent manner, significantly lowered LDL-cholesterol, triglycerides and lipoprotein(a) when added to statin. The additional reductions are clinically relevant and of the same magnitude as eprotirome given alone. Eprotirome was safe and well tolerated.

DEVELOPMENT STATUS
A third phase II study is ongoing where eprotirome is evaluated as add on to treatment with the cholesterol absorption inhibitor ezetimibe. The results will be reported in the fourth quarter of 2008.

POTENTIAL USES OF EPROTIROME   
Eprotirome has the potential to be used as second-line theraphy in patients inadequately controlled with or intolerant to statis. Patients with mixed dyslipidemia may also be suitable for treatment with eprotirome because they require simultaneous improvement of both LDL and triglyceride levels. Eprotirome may also become an alternative for those patients who have high levels of Lp(a).