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L7 RESULTS OF FIRST FOLLOW UP STUDY WITH GENE THERAPY WITH ALIPOGENE TIPARVOVEC (AMT-011) IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD)
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 1–15
L7 RESULTS OF FIRST FOLLOW UP STUDY WITH GENE THERAPY WITH ALIPOGENE TIPARVOVEC (AMT-011) IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD) D. Gaudet1 , J. de Wal2 , D. Brisson3 , N. van den Bulk2 , S. Greentree2 , 1 1 ´ J. Methot ´ . Dept of medicine, Universite´ de Montreal, Ecogene-21 and Lipid Clinic, Chicoutimi, QC, Canada, 2 Amsterdam Molecular Therapeutics (AMT) B.V., Amsterdam, The Netherlands, 3 Ecogene-21 and Lipid Clinic, Chicoutimi, QC, Canada Introduction: LPLD is an inherited disorder of lipid metabolism. LPLD results in chylomicronaemia, detectable as severe hypertriglyceridaemia. Recurrent pancreatitis is the most frequent complication, others are diabetes and increased tendency for atherosclerosis. Aims: The CT-AMT-011−01 study assessed the safety and efficacy of alipogene tiparvovec (AMT-011, Glybera® ), which contains LPLS447X , a gain of function LPL-gene mutation, in a non-replicating, non-integrating adeno-associated virus derived vector. Methods: 14 adult LPLD patients were enrolled in and received 3×1011 or 1×1012 gc/kg of alipogene tiparvovec, via a single series of IM leg injections; 12 patients received a 12 weeks’ immunosuppressant regime additionally. Patients were evaluated during 12 weeks post administration, with long term follow-up planned for 15 years. Prior to administration patients had been prospectively observed for 3−9 months. Results: Alipogene tiparvovec was well tolerated, safe and efficacious, with reduction in pancreatitis risk over the first few years now being most noticeable. An >40% reduction in fasting triglyceride (TG) levels was observed in the majority of subjects beginning 2 weeks post administration and maintained during the 12 weeks study. After approximately 4 months, TG trended back towards baseline. We will report data from routine lipoprotein/lipid analysis, which provide explanations for the previously unexpected TG. Persistent gene expression was confirmed in injected muscle tissue after half a year and clinically patients stayed well during 2 years. Conclusions: Alipogene tiparvovec gene therapy is associated with lasting changes in lipoprotein characteristics and clinical patterns. Observations from our study may add to understanding normal and pathological lipid metabolism.
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Atherosclerosis Supplements 11, no. 2 (2010) 1–15
L7 RESULTS OF FIRST FOLLOW UP STUDY WITH GENE THERAPY WITH ALIPOGENE TIPARVOVEC (AMT-011) IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD) D. Gaudet1 , J. de Wal2 , D. Brisson3 , N. van den Bulk2 , S. Greentree2 , 1 1 ´ J. Methot ´ . Dept of medicine, Universite´ de Montreal, Ecogene-21 and Lipid Clinic, Chicoutimi, QC, Canada, 2 Amsterdam Molecular Therapeutics (AMT) B.V., Amsterdam, The Netherlands, 3 Ecogene-21 and Lipid Clinic, Chicoutimi, QC, Canada Introduction: LPLD is an inherited disorder of lipid metabolism. LPLD results in chylomicronaemia, detectable as severe hypertriglyceridaemia. Recurrent pancreatitis is the most frequent complication, others are diabetes and increased tendency for atherosclerosis. Aims: The CT-AMT-011−01 study assessed the safety and efficacy of alipogene tiparvovec (AMT-011, Glybera® ), which contains LPLS447X , a gain of function LPL-gene mutation, in a non-replicating, non-integrating adeno-associated virus derived vector. Methods: 14 adult LPLD patients were enrolled in and received 3×1011 or 1×1012 gc/kg of alipogene tiparvovec, via a single series of IM leg injections; 12 patients received a 12 weeks’ immunosuppressant regime additionally. Patients were evaluated during 12 weeks post administration, with long term follow-up planned for 15 years. Prior to administration patients had been prospectively observed for 3−9 months. Results: Alipogene tiparvovec was well tolerated, safe and efficacious, with reduction in pancreatitis risk over the first few years now being most noticeable. An >40% reduction in fasting triglyceride (TG) levels was observed in the majority of subjects beginning 2 weeks post administration and maintained during the 12 weeks study. After approximately 4 months, TG trended back towards baseline. We will report data from routine lipoprotein/lipid analysis, which provide explanations for the previously unexpected TG. Persistent gene expression was confirmed in injected muscle tissue after half a year and clinically patients stayed well during 2 years. Conclusions: Alipogene tiparvovec gene therapy is associated with lasting changes in lipoprotein characteristics and clinical patterns. Observations from our study may add to understanding normal and pathological lipid metabolism.
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