Treating Homozygous Familial Hypercholesterolemia (HoFH)
Homozygous familial hypercholesterolemia (HoFH) is a rare form of familial hypercholesterolemia (FH). It impacts roughly 1 in 300,000 people in the United States and worldwide. Someone with HoFH has inherited one FH gene from each of their parents.
This condition typically leads to untreated LDL-Cholesterol (LDL) levels between 400 mg/dl and 1000 mg/dl – sometimes even higher. If cholesterol this high remains untreated, people with HoFH are at risk of developing premature heart disease. Most individuals with HoFH can’t lower their LDL enough with one, two, or even three cholesterol lowering medications.
HoFH and LDL Receptors
As new medications have been developed, people with HoFH have incrementally improved their LDL. Existing treatments like statins, ezetimibe, and PCSK9 inhibitors have one thing in common – they increase the number of LDL receptors (LDLRs) a person has on their liver and other cells. The more LDLRs a person has, the more efficiently they remove LDL from their blood. This effectively lowers their LDL levels.
The problem is that most people with HoFH have dysfunctional or non-functioning LDLRs. As a result, these individuals don’t respond well enough to these medications.
A Treatment for Homozygous Familial Hypercholesterolemia
Enter lomitipide (brand name Juxtapid). This treatment was approved by the Food and Drug Administration (FDA) in 2012 for LDL reduction in people with HoFH.
What’s important to know about lomitapide is that it doesn’t require functioning LDLRs. Lomitipide prevents the liver from secreting very low-density lipoprotein (VLDL) into the blood. Normally, VLDL is converted to LDL, so when the VLDL is reduced in the blood, less LDL is produced.
Studies have shown that lomitipide reduces LDL, on average, by 40%. This, on top of other lipid lowering medications, has helped people with HoFH normalize their LDL levels.