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.
Nitisinone is in clinical development for the treatment of alkaptonuria. Alkaptonuria is a rare metabolic disorder, in which patients lack a functional enzyme that prevents the body fully breaking down two amino acids called tyrosine and phenylalanine. This results in a build-up of a chemical called homogentisic acid (HGA) in the body, which is deposited as black pigment in tissues, in a process called ochronosis. This results in dark colouration of urine, joint problems, breathing difficulties and heart, kidney and prostate problems. In the later stage, patients may experience physical disability and inability to perform daily activities. Early recognition and management of alkaptonuria is desirable to slow the progression of this disease.