Homozygous Familial Hypercholesterolaemia
Homozygous Familial Hypercholesterolaemia (HoFH) is a rare and severe genetic disease, causing excessive levels of low-density lipoprotein cholesterol (LDL-C) or ‘bad cholesterol’ to accumulate in the body from conception. Healthy levels of this ‘bad cholesterol’ are typically in the range of 3 mmol/L; however babies with HoFH can be born with ‘bad cholesterol’ levels as high as 20 mmol/L. The cholesterol levels are high as the receptors in the liver that remove excess cholesterol from the blood stream, the LDL-receptors, don’t work properly due to the mutations in genes that are involved in making the receptors.
The high levels of cholesterol means that the cholesterol rapidly accumulates and deposits throughout the body as fatty lumps under the skin and on the muscle tendons (xanthomas), around the eyes (xanthelasma) but most importantly in the cardiovascular system resulting in severe and progressive atherosclerosis.
Current standard of care includes lifestyle management (diet, exercise), lipid-lowering treatments including statins, ezetimibe, bile acid sequestrants, and new drugs like PCSK9 inhibitors.
Most of these lipid-lowering treatments work through the LDL Receptor in the liver to try to clear the blood stream of the high levels of cholesterol. But as these receptors don’t work properly in HoFH, due to the underlying genetic mutations, they have limited effect in lowering ‘bad cholesterol’ levels in HoFH patients.
Another therapy is available, which involves the mechanical removal of cholesterol from the bloodstream through a process similar to dialysis called lipoprotein apheresis (LA). While LA can be effective in lowering cholesterol in the acute setting, cholesterol levels rebound rapidly returning to 50% of their original levels by day 3 and to baseline levels by day 7. Therefore, although the combination of statins, ezetimibe and PCSK9 inhibitors and LA may lower cholesterol levels to an extent, these treatments will not result in consistent and maintained lowering to recommended target levels. As such patients with HoFH still have high cholesterol levels and are at a continued risk of progressive atherosclerotic disease and life-threatening cardiac events, for example, heart attack, stroke, major cardiac surgery and premature cardiac death.
Amryt Pharma holds the marketing authorisation for Lojuxta®▼ and Juxtapid® (lomitapide) for adult patients with HoFH across the North America, Latin America, EEA, Middle East, North Africa, Turkey and Israel. It is a prescription medicine used along with diet and other lipid-lowering treatments, including low-density lipoprotein (LDL) apheresis where available, in adults with homozygous familial hypercholesterolemia (HoFH).
When HoFH affects a whole family: remembering Rianna
In this story, both parents have heterozygous FH and each have a single faulty gene causing FH, but sometimes children like Rianna inherit a faulty copy of the genes, one from each parent (a ‘double dose’) and have HoFH. Unfortunately Rianna wasn’t formally diagnosed with HoFH and wasn’t receiving any treatment. Had Rianna been diagnosed, potential treatments may have included statins, ezetimibe and apheresis. The video highlights the need for early diagnosis and treatment of individuals with HoFH.
Living with extreme levels of cholesterol: a family’s story of HoFH
In this story, the Kara/Mehter family suffers with either homozygous familial hypercholesterolaemia (HoFH) or the heterozygous type (HeFH), life-threatening genetic disorders where you have extreme levels of cholesterol from birth. Zunairah (7), Abida (26), Farhana (35) and Mohammed (43) talk about being diagnosed and their weekly or fortnightly experience with apheresis – a ‘dialysis for cholesterol’, which is a long and exhausting treatment, deeply affecting the day-to-day life of people with HoFH and their carers. Like the Wingett family in the video above, the Kara/Mehter family advocates for improved awareness as well as access to new treatments – a vital step for HoFH sufferers.
Homozygous Familial Hypercholesterolaemia is a genetic condition that children inherit from both their parents.
It is estimated that ~1.5 HoFH patients per million of population may be clinically diagnosed, with many more in some countries, either due to the founder mutations in the gene pool or the number of marriages within families.
People with HoFH can have 10 times the target level of cholesterol in their blood. It inevitably leads to severe heart disease and people with HoFH have an average life expectancy of just 45 years even if they are treated with current standard of care. This is more than 30 years shorter than the European average of 82 years.
Left untreated, by the time children with HoFH are ~12 years old, they will likely have reached their cholesterol exposure for cardiovascular disease. This normally would not happen until a person was 60-70 years old. Children who reach this threshold have an early and severe risk of heart attacks, strokes, major heart disease and premature death, often in the first decade of their life, if they are not properly diagnosed and receiving treatment.
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Reporting forms and information can be found on the MHRA Yellow Card reporting site.
Adverse events should also be reported to Amryt Pharmaceuticals DAC on:
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