Safety and Efficacy in LPL-Deficient Subjects of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein Lipase [S447X]

LPLD is a rare autosomal recessive disorder, characterized by the presence of marked chylomicronemia and hence hypertriglyceridemia. Clinically the most severe manifestation of chylomicronemia, is acute pancreatitis, which can be lethal. There is no effective therapy available to modulate the course of the illness and prevent complications for these patients. The current clinical management consists of severe reduction of dietary fat that is hard if not almost impossible to comply with. LPLD subjects continue to experience pancreatitis attacks, and are admitted to intensive care units on several occasions. Alipogene tiparvovec corrects or restores lipoprotein lipase (LPL) function long term, and hence reverses some symptoms, halts the disease progression and prevents further complications. Alipogene tiparvovec gene therapy ensures that a catabolically beneficial variant of the human LPL gene, LPL\[S447X\] is expressed and active in the relevant tissues in humans. Delivery of the gene is realized via intramuscular injection of an adeno-associated viral vector, pseudotyped with AAV1 capsids.