Date: 2015-05-26
Type of information: Results
phase: 3
Announcement: results
Company: Aegerion Pharmaceuticals (USA - MA)
Product: lomitapide
Action
mechanism: protein inhibitor/microsomal triglyceride transfer protein (MTP) inhibitor. Lomitapide is a small molecule, microsomal triglyceride transfer protein inhibitor, or MTP-I. HoFH is a rare genetic disorder inherited from both parents, and characterised by significantly elevated low density lipoprotein cholesterol (LDL-C) levels. HoFH patients have LDL receptors that are either non-functional or are defective in their functioning. Patients diagnosed with HoFH typically have as much as three to six times the normal amount of LDL-C while on a variety of lipid-lowering drug treatments, putting them at risk for a major cardiovascular event. Most other drug treatments such as statins work by increasing the number of LDL-receptors and if these are defective or negative, the drugs that work by these mechanisms typically have limited effectiveness in HoFH patients. Inhibition of MTP reduces lipoprotein secretion and circulating concentrations of lipoprotein-borne lipids including cholesterol and triglycerides.
Disease: homozygous familial hypercholesterolemia (HoFH)
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases
Country: Japan
Trial details:
Latest
news: * On May 26, 2015, Aegerion Pharmaceuticals announced the primary endpoint was achieved in the open-label, multicenter study to evaluate the efficacy and safety of lomitapide in nine Japanese patients with homozygous familial hypercholesterolemia (HoFH). The primary endpoint measured mean percent change in low-density lipoprotein cholesterol (LDL-C) at the maximum tolerated dose compared to baseline after 26 weeks of treatment, in combination with other lipid-lowering therapy. These data will serve as the basis of theJapanese new drug application for lomitapide in adult HoFH patients which Aegerion expectq to file late in the fourth quarter of 2015 or early in the first quarter of 2016. Following the 26 week assessment, patients in the study entered a 30-week safety phase. Each patient will continue receiving the maximum tolerated dose of lomitapide he or she achieved during the efficacy phase for an additional 30 weeks in the safety phase, subject to safety-related dose adjustments. The Company expects to file the NDA in Japan with the 26-week data, and to submit the 56-week data during the review cycle. * On April 9, 2014, Aegerion Pharmaceuticals announced that patient enrollment has been initiated in Japan in a clinical trial of lomitapide as an adjunct treatment to reduce low-density lipoprotein cholesterol (LDL-C) in Japanese patients with homozygous familial hypercholesterolemia (HoFH). Last year, Aegerion received orphan drug designation from Japan\'s Ministry of Health, Labour and Welfare for lomitapide.
The phase 3, open-label trial in Japan is similar in design to the completed Phase 3 trial conducted in the United States and other countries. Estimated enrollment is between five and 10 adult HoFH patients who are receiving concomitant lipid-lowering therapies, including, in some cases, apheresis. After a six week run-in period, patients will receive lomitapide for 26 weeks, starting at 5 mg/day and escalating to a maximum dose of 60 mg based on tolerability. After 26 weeks, patients will enter a 30 week safety phase. The primary endpoint is % change in LDL-C levels from baseline to week 26. Secondary endpoints include % change in lipid parameters, long-term safety, and changes in hepatic fat from baseline to week 56. The Japanese regulatory authorities (PMDA) have indicated they will allow the new drug application to be filed following completion of the 26 week efficacy phase.
