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Abstract: P475 SAFETY AND EFFICACY OF AMT-010 GENE THERAPY IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD)
Poster - PHARMACOLOGY OF CVD - Novel Therapies Abstract: P475 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
SAFETY AND EFFICACY OF AMT-010 GENE THERAPY IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD) E Stroes1, J Kuivenhoven1, S van Deventer2, J Kastelein1 1
Vasc Med, AMC, Amsterdam; 2Clin Dev, AMT, Amsterdam
Objectives To study if AMT-010 prevents complications of LPLD. In LPLD an LPL gene mutation results in (almost) total LPL activity loss in homozygotes or compound heterozygotes (H/H). LPL's primary function is to offload triglycerides (TG) from chylomicrons (CM). Pancreatitis is the most frequent complication. Alipogene tiparvovec, the first LPLD therapy in development, contains a human gene variant, LPLS447X, in a non-replicating non-integrating adeno-associated vector. AMT-010 is similar, but was produced using a plasmid based, not a recombinant baculovirus expression system. Methods We conducted an observational study (PREP-01) and an open-label study with AMT-010 (CTAMT-010). 18 LPL activity deficient subjects with a pancreatitis history were enrolled in PREP-01, of which 8 H/H were treated during CT-AMT-010, 4 with 1x1011 and 4 with 3x1011 gc/kg via a single series of IM leg injections. Patients kept a low fat and alcohol free diet during the studies. AEs, including pancreatitis, were recorded. Pancreatitis incidence was calculated using mixed nonlinear model. Safety and efficacy of AMT-010 was evaluated over a period of 12 weeks[1] with follow-up (FU) planned for 5 years. Half a year post-dosing muscle biopsies were taken. Here we report 2-3 years FU. Results Pancreatitis incidence decreased from 0.49 (H/H in PREP-01) to 0.04 episodes/yr (CT-AMT010) (p=0.05), despite a rise of TG. Vector DNA and LPLS447X expression was present in muscle. No safety issues with AMT-010 were noted during this FU. Conclusions A single dose of AMT-010 was safe and effective to prevent recurrent pancreatitis, most likely through continued expression of LPLS447X. [1] E.S. Stroes et al. Arterioscler Thromb Vasc Biol. 2008 28(12):2303-4. Funding: AMT sponsored study.
SAFETY AND EFFICACY OF AMT-010 GENE THERAPY IN LIPOPROTEIN LIPASE DEFICIENCY (LPLD) E Stroes1, J Kuivenhoven1, S van Deventer2, J Kastelein1 1
Vasc Med, AMC, Amsterdam; 2Clin Dev, AMT, Amsterdam
Objectives To study if AMT-010 prevents complications of LPLD. In LPLD an LPL gene mutation results in (almost) total LPL activity loss in homozygotes or compound heterozygotes (H/H). LPL's primary function is to offload triglycerides (TG) from chylomicrons (CM). Pancreatitis is the most frequent complication. Alipogene tiparvovec, the first LPLD therapy in development, contains a human gene variant, LPLS447X, in a non-replicating non-integrating adeno-associated vector. AMT-010 is similar, but was produced using a plasmid based, not a recombinant baculovirus expression system. Methods We conducted an observational study (PREP-01) and an open-label study with AMT-010 (CTAMT-010). 18 LPL activity deficient subjects with a pancreatitis history were enrolled in PREP-01, of which 8 H/H were treated during CT-AMT-010, 4 with 1x1011 and 4 with 3x1011 gc/kg via a single series of IM leg injections. Patients kept a low fat and alcohol free diet during the studies. AEs, including pancreatitis, were recorded. Pancreatitis incidence was calculated using mixed nonlinear model. Safety and efficacy of AMT-010 was evaluated over a period of 12 weeks[1] with follow-up (FU) planned for 5 years. Half a year post-dosing muscle biopsies were taken. Here we report 2-3 years FU. Results Pancreatitis incidence decreased from 0.49 (H/H in PREP-01) to 0.04 episodes/yr (CT-AMT010) (p=0.05), despite a rise of TG. Vector DNA and LPLS447X expression was present in muscle. No safety issues with AMT-010 were noted during this FU. Conclusions A single dose of AMT-010 was safe and effective to prevent recurrent pancreatitis, most likely through continued expression of LPLS447X. [1] E.S. Stroes et al. Arterioscler Thromb Vasc Biol. 2008 28(12):2303-4. Funding: AMT sponsored study.