Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. A study has assessed the efficacy and safety of the microsomal triglyceride transfer protein ( MTP ) inhibitor, Lomitapide ( Juxtapid, Lojuxta ), in adults with this disease.
Researchers did a single-arm, open-label, phase 3 study of Lomitapide for treatment of patients with homozygous familial hypercholesterolemia.
Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day.
The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on Lomitapide through to week 78 for safety assessment.
29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries ( USA, Canada, South Africa, and Italy ). 23 of 29 enrolled patients completed both the efficacy phase ( 26 weeks ) and the full study ( 78 weeks ).
The median dose of Lomitapide was 40 mg a day.
LDL cholesterol was reduced by 50% from baseline ( mean 8.7 mmol/L ) to week 26 ( 4.3 mmol/L; p less than 0.0001 ).
Levels of LDL cholesterol were lower than 2.6 mmol/L in eight patients at 26 weeks.
Concentrations of LDL cholesterol remained reduced by 44% ( p less than 0.0001 ) at week 56 and 38% ( -52 to -24; p less than 0.0001 ) at week 78.
Gastrointestinal symptoms were the most common adverse event. Four patients had aminotransaminase levels of more than five times the upper limit of normal, which resolved after dose reduction or temporary interruption of Lomitapide.
No patient permanently discontinued treatment because of liver abnormalities.
The study suggests that treatment with Lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia. ( Xagena )
Cuchel M et al, The Lancet 2013; 381: 40-46