Alipogene tiparvovec for the treatment of lipoprotein lipase deficiency.

Alipogene tiparvovec is the first adeno-associated virus (AAV)-mediated gene therapy to be approved for the treatment of a metabolic disorder. Lipoprotein lipase (LPL) deficiency (LPLD) is a rare autosomal-recessive disorder in which gene mutations cause the production of a catalytically inactive enzyme required for plasma triglyceride hydrolysis. The resultant hypertriglyceridemia causes frequent abdominal pain, fatty deposits in the skin and retina, and can lead to potentially fatal pancreatitis. In addition, patients with LPLD can develop diabetes and cardiovascular disease. Past therapies to lower plasma triglycerides in these patients have been ineffective. Intramuscular injection of alipogene tiparvovec delivers a natural gain-of-function LPL gene variant, LPLS447X, to muscle tissue and has demonstrated efficacy in animal models of LPLD. In phase I/II and phase II/III clinical evaluations, alipogene tiparvovec significantly lowered plasma triglycerides and increased LPL activity, resulting in a reduction in plasma chylomicron and a decrease in the frequency of pancreatitis episodes. The therapy is well tolerated in animals and humans and produces no serious treatment-related adverse effects.