Abstract 17396: Apheresis Treatment does not Affect the Lipid-Lowering Efficacy of Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Patients with Homozygous Familial Hypercholesterolemia

Abstract

BACKGROUND: Patients with Homozygous Familial Hypercholesterolemia (HoFH) are at very high risk for premature cardiovascular disease and are refractory to existing lipid lowering drug therapy. Apheresis is considered standard of care for this condition. Lomitapide, a microsomal triglyceride transfer protein inhibitor, is currently under investigation for treatment of adults with HoFH. Previously reported results from the phase 3 study indicated that, in those who completed the efficacy phase, lomitapide significantly reduced LDL-C by about 50%. We report here results from a post hoc analysis to evaluate if apheresis treatment affects its lipid-lowering efficacy.

METHODS: HoFH patients were enrolled into a single arm, open label study during which they were instructed to continue current lipid lowering therapy, including apheresis, unchanged from six weeks prior to baseline through week 26, the end of the efficacy phase. The primary endpoint was mean percent change from baseline of LDL-C at week 26 (intent to treat analysis). A mixed-models repeated measures analysis was used for analysis of the data. RESULTS: Of the 29 HoFH subjects enrolled, 18 were receiving either plasma or LDL apheresis and 11 were not. Twenty-three subjects (13 receiving apheresis) completed the week 26 evaluation. Baseline LDL-C levels in patients on apheresis and patients not on apheresis were 326± 108 mg/dL vs. 355 ± 125 mg/dL, respectively. LDL-C levels were reduced by 48% in subjects undergoing apheresis treatment and by 55% in subjects not on apheresis treatment (p=0.54). Similarly, no difference was observed for apo B (-48% vs. -53%, p=0.62), total cholesterol (-44% vs. -50%, p=0.58), triglycerides (-45% vs. -41%, p=0.78) or other lipoprotein parameters. CONCLUSIONS: These data indicate that lomitapide markedly reduced LDL-C and other apoB-containing lipoprotein parameters in patients with HoFH and its efficacy was independent of the use of apheresis treatment.