Treating Severely Elevated Cholesterol Levels
Our lead product compound, lomitapide, is a small molecule microsomal triglyceride transfer protein inhibitor, or MTP-I, that we are developing as an oral, once-a-day treatment for patients with severe lipid disorders. Lomitapide is being evaluated for its ability to reduce low density lipoprotein (LDL-C) or bad cholesterol levels in patients with HoFH and reduce triglyceride (TG) levels in patients with a severe form of hypertriglyceridemia called FC. It works by reducing lipid levels in the blood by preventing the liver and intestines from secreting lipids into the blood stream. In addition to an ongoing pivotal Phase III clinical trial, lomitapide has been evaluated in seven Phase I and six Phase II clinical trials.
Orphan Drug Status
Lomitapide was granted orphan drug designation by the FDA in the US for the treatment of HoFH and FC, and by the European Medicines Agency, EMA for the treatment of FC.
Aegerion is conducting clinical trials to determine the safety, efficacy and tolerability of its lead candidate lomitapide, a small molecule, MTP-I inhibitor being developed as an oral, once-a-day treatment for rare genetic lipid disorders. Overall, lomitapide has been evaluated in seven Phase I and six Phase II clinical trials. A total of 703 patients were treated with lomitapide in these Phase I and Phase II trials.
Aegerion has an ongoing, pivotal, Phase III clinical trial to determine the efficacy and long-term safety of lomitapide for the treatment of patients with homozygous familial hypercholesterolemia, or HoFH.
Pivotal Phase III Trial in HOFH
Aegerion is conducting a pivotal, single arm, open-label Phase III clinical trial to evaluate the efficacy and long-term safety of lomitapide for the treatment of patients with HoFH at the maximum tolerated dose of up to 60 mg. The Phase III study is being conducted at 11 sites in four countries and is fully-enrolled with 29 patients. The patients are adult males and females with a mean age of 30.6 years. After a six week run-in period on current lipid lowering therapy, including, statins and apheresis, if applicable, patients received ascending doses of lomitapide titrated over the first 26 weeks of the trial to as much as 60 mg/day. The mean patient dose was 43 mg. Patients will remain on their highest tolerated dose for an additional 52 week safety phase. The efficacy and safety phases combined will last 78 weeks.
Primary Efficacy Endpoint
The primary efficacy endpoint of this trial is percent change in LDL-C at the maximum tolerated dose of lomitapide compared to baseline after 26 weeks of treatment in combination with other lipid lowering therapies. As of the end of September 2010, all 23 patients remaining in the trial had completed the 26 week efficacy phase of the trial. The results indicate patients experienced a mean LDL-C reduction (50% CA / 45% ITT) on top of background therapy as well as a median triglyceride reduction of (54% CA / 45% ITT) in comparison to baseline.
Three patients discontinued the study due to GI Adverse Events and three patients withdrew consent. Mild-to-moderate gastrointestinal adverse events have been the most commonly reported side effect in this trial. Aegerion expects to complete the safety phase of this trial in the second half of 2011. The Company plans to submit an NDA to the FDA before the end of 2011.
You can view further details of this trial on ClinicalTrials.gov or for other Aegerion clinical trial information, visit our Physician and Patient Center.