What are we able to achieve today for our patients with homozygous familial hypercholesterolaemia, and what are the unmet needs?

Homozygous familial hypercholesterolaemia (HoFH) is a rare, life-threatening disease characterised by highly elevated low-density lipoprotein cholesterol levels (LDL-C), cutaneous and tendinous xanthomata, severe and precocious atherosclerosis, and aortic and supra aortic valve disease. Although treatment with apheresis and lipid-lowering drugs has improved event-free survival of HoFH patients, the condition is still associated with early onset cardiovascular disease and death due to residual high cholesterol levels. Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are powerful cholesterol-lowering agents, but HoFH patients are often inadequately controlled on statins alone; therefore, a variety of other medications, including the cholesterol absorption inhibitor ezetimibe, bile acid sequestrants and niacin, have been used to try to achieve recommended LDL-C goals. However, even in patients with access to the best available treatments, HoFH has continued to be associated with extreme rates of morbidity and premature mortality. The microsomal triglyceride transfer protein inhibitor lomitapide has recently received regulatory approval in the European Union and the United States of America for use in patients with HoFH and a number of other agents are currently in development, including apolipoprotein B antisense oligonucleotides (approved in the US), and proprotein convertase subtilisin kexin type 9 (PCSK-9) inhibitors. These new approaches may result in improved clinical outcomes for HoFH patients. In the future it will be important to begin treatment early and to treat as aggressively as possible.