Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia.
New lipid-lowering agents include microsomal triglyceride transfer protein (MTP) inhibitors, which may have a role in the treatment of hypercholesterolemia. Clinical applications of MTP inhibitors have been focused primarily on high-dose monotherapy to produce substantial reductions in LDL-cholesterol levels (particularly for patients with homozygous familial hypercholesterolemia). However, this strategy has been associated with a high rate and severity of gastrointestinal and hepatic adverse events that has prohibited the use of these agents. Data suggest the LDL-cholesterol-lowering efficacy of low-dose lomitapide (AEGR-733, formerly BMS-201038), under development by Aegerion Pharmaceuticals Inc, in patients with familial hypercholesterolemia, both as a single agent and in combination with commonly prescribed lipid-lowering therapies. MTP inhibition with lomitapide may offer a treatment option for patients who cannot tolerate statin therapy or who experience insufficient LDL-cholesterol reduction with available therapies. However, the safety concerns for MTP inhibitors for the treatment of hyperlipidemia must be fully addressed, and the assessment of the risk-to-benefit ratio for MTP inhibitors in patients at different levels of cardiovascular-disease risk is required before clinical use of this class of drugs may be recommended.
Rizzo
Manfredi
M
University of Palermo, Department of Internal Medicine and Emerging Diseases, Via del Vespro 141, 90127 Palermo, Italy. mrizzo@unipa.it
D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology
D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D002352:Carrier Proteins; D008078:Cholesterol, LDL; C106092:microsomal triglyceride transfer protein