This week, Regeneron Pharmaceuticals announced that their Biologics License Application (BLA) for evanicumab, a treatment for homozygous familial hypercholesterolemia (HoFH), was granted Priority Review status by the FDA. The investigational therapy could be used in conjunction with other lipid-lowering treatments, providing relief for patients.
Familial hypercholesterolemia (FH) is an inherited form of extremely high cholesterol. Currently, it has two main subtypes: heterozygous (HeFH) and homozygous (HoFH). Patients with HoFH require two LDLR, APOB, or PCSK9 gene mutations; those with HeFH require only one. Approximately 1,300 American citizens have HoFH. People with Afrikaan, French Canadian, Lebanese, and Finnish backgrounds have a higher risk of inheriting this condition.
According to the American Heart Association, cholesterol is:
a waxy substance [that comes from] your liver [and] foods derived by animals.
This substance plays a role in hormone and cell membrane development, as well as fat digestion. But too much cholesterol, warns the AHA, can:
form a thick, hard deposit on the inside of the arteries, [narrowing the arteries and making them less flexible], – a condition known as atherosclerosis. If a blood clot forms and blocks one of these narrowed arteries, a heart attack or stroke can result.
Patients with HoFH often have excessively high levels of a “bad” form of cholesterol called low-density lipoprotein cholesterol, or LDL-C. This is because receptors in their blood stream are defective or missing. As a result, cholesterol accumulates in blood. Generally, HoFH is resistant to treatments, like statins, which are normally used to treat high cholesterol.
- Coronary artery disease
- Chest pain
- Xanthomas, or collections of cholesterol buildup, on hand, finger, and heel tendons
- Cholesterol buildup around the eyelids
- Heart attacks
Learn more about HoFH here.
To create evinacumab, Regeneron used their proprietary VelocImmune® platform. Through this, Regeneron creates human monoclonal antibodies through a genetically-modified mouse platform with humanized immune systems. The therapy, an investigational monoclonal antibody, inhibits angiopoietin-like 3 (ANGPTL3). Previously, reducing ANGPTL3 function was shown to also reduce lipid levels, such as LDL-C.
The efficacy of evinacumab is currently being studied in a Phase 3 extension trial, following positive data from the Phase 3 ELIPSE trial. During that trial, 65 patients with HoFH received either a placebo or intravenous injections of 15mg/kg evinacumab every 4 weeks for a 5.5 month period. Trial results are published here.
Ultimately, evinacumab was shown to reduce LDL-C levels in patients better than prior treatment options. The FDA aims to respond to the BLA in full by February 2021.