The Lomitapide Story

Beginning in the mid-to-late 1990s, Bristol Myers Squibb (BMS) began development of the small molecule, microsomal triglyceride transfer protein MTP inhibitor, lomitapide as a monotherapy to replace statins for the treatment of elevated cholesterol and triglycerides. Early clinical trials produced meaningful reductions in LDL-C levels but participants discontinued use at a high rate due to gastrointestinal side effects. These findings would have greatly limited the addressable broad market on which BMS was focusing its development. At the time, BMS, like many in big pharma, was not interested in developing orphan or combination therapies.

In 2003, BMS donated the molecule to Dr. Daniel J. Rader,MD, at the University of Pennsylvania (UPenn) for further study in patients with severe cholesterol problems such as HoFH. Dr. Rader is an internationally recognized leader in translational research in the areas of cholesterol metabolism and heart disease prevention. He serves as the Director of the Translational Research Center, Director of Preventive Cardiovascular Medicine and Lipid Clinic and the Director of the Lipid-Atherosclerosis Research Unit at the University of Pennsylvania. He conducted the Phase II proof-of-concept study which demonstrated that targeted inhibition of MTP is highly effective in reducing cholesterol levels in these very high risk patients. Patients in the study had a remarkable 51% reduction in low-density lipoprotein (LDL) or “bad cholesterol” levels and 65% reduction in triglycerides. This research was published in the New England Journal of Medicine in 2007.

Aegerion in-licensed lomitapide from UPenn in 2006 and with the benefit of Dr. Rader’s wisdom and knowledge redirected the product as a treatment for a devastating orphan disease, HoFH. Since then the clinical development program for lomitapide has been focused on employing a controlled-dose approach through titration, and using lower doses of lomitapide in combination with recognized lipid-lowering treatments along with a low-fat diet. Aegerion is currently completing a pivotal, Phase III clinical trial to evaluate the efficacy and long-term safety of lomitapide for the treatment of patients with HoFH.