Evinacumab is in clinical development for the treatment of homozygous familial hypercholesterolemia (HoFH). Familial hypercholestrolaemia (FH) is an inherited condition where a person’s cholesterol levels are higher than normal from birth as the liver is unable to break down or remove excess cholesterol. Specifically, FH patients have severe elevations in low density lipoprotein cholesterol (LDL-C) levels. This can lead to heart disease at a relatively young age. HoFH is a very rare and severe form of the disease which results from inheriting a faulty gene from both parents resulting in little or no LDL receptor activity. Treatment of hypercholesterolemia in patients with HoFH can be challenging with the current therapies and there is need for new treatments.
Evinacumab is a monoclonal antibody to angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 is produced in the liver and regulates levels of triglycerides, LDL-C, and high-density lipoprotein cholesterol, in the blood. Evinacumab binds to and inhibits ANGPTL3 and lowers cholesterol thereby having the potential to reduce cardiovascular risk. Results from early studies have shown that evinacumab has the potential to result in clinically significant LDL-C reductions in HoFH patients.
Migalastat works by stabilizing the body’s own dysfunctional enzyme, so it can clear the accumulated disease substrate in patients who have amenable mutations. Migalastat is currently licenced for patients aged 16 or over with Fabry disease and an amenable mutation. If the license is extended, migalastat may offer an additional treatment option for paediatric subjects 12 to 15 years old with Fabry disease and an amenable mutation, who weight over 45Kgs.