Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial

We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPLS447X gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPLS447X gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a >= 40% reduction in fasting median plasma triglyceride (TG) at 3-12 weeks compared with baseline. Cohorts 1 (n = 2) and 2 (n = 4) received 3 x 10(11) gc kg(-1), and cohort 3 (n = 8) received 1 x 10(12) gc kg(-1). Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a >= 40% reduction in fasting TG between 3 and 12 weeks. TG subsequently returned to baseline, although sustained LPLS447X expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG. Gene Therapy (2013) 20, 361-369; doi: 10.1038/gt.2012.43; published online 21 June 2012