Abstract 16516: Sustained LDL-C Lowering and Stable Hepatic Fat Levels in Patients With Homozygous Familial Hypercholesterolemia Treated With the Microsomal Triglyceride Transfer Protein Inhibitor, Lomitapide: Results of an Ongoing Long-Term Extension Study
Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by markedly elevated LDL-C and high CVD risk. Lomitapide is approved in the US to lower LDL-C as an adjunct to other lipid lowering agents, including apheresis, for adults with HoFH. We report efficacy and safety findings from a long term extension study in patients treated with lomitapide for 2.5-4.5 years.
Methods: Following the pivotal 78 week study, eligible patients entered an open label extension phase and continued lomitapide at their maximum tolerated dose. The primary efficacy endpoint was mean % change in LDL-C from baseline to week 126 (~2.5 years). Safety endpoints included assessment of hepatic fat as measured by nuclear magnetic resonance spectroscopy (NMRS), liver function tests, and adverse events (AEs).
Results: Nineteen of 23 patients who completed the pivotal study entered the extension study. Follow-up ranged from ~2.5 - 4.5 years. LDL-C levels were reduced by 45.5% at week 126 (356 ± 127 mg /dL vs. 189 ± 120 mg/dL; P <0.001). Similar mean % reductions were observed for Apo B -54%, non-HDL-C -47%, VLDL-C -37%, and triglycerides -53% (median), (P ≤0.006 for all). At any time on study, an LDL-C of ≤ 100 or ≤ 70 mg/dL was achieved by 13 (68%) and 9 (47%) patients, respectively. Median hepatic fat levels were 6.5% at entry to the extension phase and remained stable over 2 years (median 7.7% (range 0.6, 35.2)). Transient aminotransferase elevations >5x ULN occurred in 4 patients; 1 patient had a reversible ALT elevation of 24x ULN following co-prescription of agomelatine and a potent inhibitor of CYP3A4 (clarithromycin); 1 other patient, who use excessive alcohol, was withdrawn due to persistent ALT elevations >5x ULN. No Hy’s law cases were reported. The AE profile in patients who continued on the extension study was similar to the pivotal trial. GI symptoms were the most common AEs,observed in 63% (12/19) of patients in the extension study. One sudden cardiac death occurred in a 58 year old patient with known CAD.
Conclusions: Results of the ongoing extension study are consistent with those observed in the pivotal study and demonstrate sustained efficacy and an acceptable longer-term safety profile of lomitapide in patients with HoFH.
- © 2013 by American Heart Association, Inc.