Scott_2015_Drugs_75_175

Alipogene tiparvovec (Glybera(R); AMT-011, AAV1-LPL(S447X)) is an adeno-associated virus serotype 1-based gene therapy for adult patients with familial lipoprotein lipase (LPL) deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It is administered as a one-time series of intramuscular injections in the legs. LPLD, a rare autosomal recessive disorder, results in hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, the most debilitating of which is recurrent severe and potentially life-threatening pancreatitis. In clinical studies (n = 27 patients), one-time administration of alipogene tiparvovec was associated with significant reductions in plasma triglyceride levels during the 12 or 14 week study period post administration. Although triglyceride levels returned to pre-treatment levels within 16-26 weeks after administration, patients had sustained improvements in postprandial chylomicron metabolism, with sustained expression of functional copies of the LPL (S477X) gene and of biologically active LPL in skeletal muscle. Moreover, after up to 6 years' follow-up post administration, there were clinically relevant reductions in the incidence of documented pancreatitis and acute abdominal pain events consistent with pancreatitis. Alipogene tiparvovec was generally well tolerated, with most adverse events being localized, transient, mild to moderate injection-site reactions. This article reviews the pharmacology of alipogene tiparvovec and its efficacy and safety in adults with LPLD.