Eprotirome (KB2115) - dyslipidemia

The thyroid hormone is one of the body’s own ways of regulating lipids in the blood. Most of this effect is exercised in the liver. Eprotirome is a novel, liver selective thyroid hormone receptor agonist for the treatment of dyslipidemia. Eprotirome’s profile is unique. In one single compound, powerful reductions of several independent risk factors for the development of atherosclerotic cardiovascular diseases are combined.

In the clinical phase II studies, eprotirome has shown statistically significant and clinically relevant reductions of LDL-cholesterol, non-HDL cholesterol, apoB, triglycerides and lipoprotein(a). The effects are of the same magnitude whether eprotirome is given as monotherapy or as add-on to statins or ezetimibe. Karo Bio has also generated pre-clinical data that indicate that eprotirome has positive effects on blood glucose. This would be of additional value when treating type 2 diabetics suffering from elevated blood lipids. Eprotirome has been well tolerated in the clinical studies of up to three months duration.

The treatment of dyslipidemia is initiated in order to reduce the risk for heart attack and stroke. The efficacy profile of eprotirome suggests that the compound is suitable as an add-on treatment for the large number of patients that do not reach their treatment targets with existing therapies. The statins have become the largest pharmaceutical category in the world and will continue to form the basic treatment of dyslipidemia.

Eprotirome is expected to be used primarily as add-on to statins and to compete with ezetimibe, nicotinic acid, fibrates, and omega-3 fatty acids. The market is projected to be driven primarily by the specialist physicians treating patient groups with high or very high risk. It is Karo Bio’s belief that the effect profile of eprotirome is very attractive compared to its competitors, and the potential for commercial success is good. The compilation and analysis of data from the supplementary pre-clinical and clinical studies carried out in 2009 is ongoing. The preliminary analysis of data from these studies looks as expected and supports eprotirome’s continued development to be a drug.

Karo Bio continues to have discussions with potential partners for eprotirome. In parallel, regulatory aspects of the continued clinical development are being investigated. It is important to receive a clarification of what the regulatory authorities, primarily the FDA in the US and EMA in Europe, can be expected to require for an eventual marketing approval of the drug. The expected regulatory demands define the size and cost of the phase III program, as well as the initial labeling of the drug.

For a successful partnership, it is important to define a clear development path that is agreed with the authorities, and for which costs, timelines, risks and opportunities can be estimated. The timeline for the dialogue and information exchange with the authorities is dependent on the clarification of all outstanding questions in a way that satisfies both parties.

An attractive business plan can also be based on a more limited indication. An initial niche indication can potentially be extended to broader patient groups when more data is gradually generated. Depending on the agreements with the authorities, a clinical phase III program can be initiated in either Europe or the US, and at later stage be extended.