Ecogene 21

Published purpose

The current project aims at obtaining relevant data to select the targeted population and clinical biomarkers for the long-term monitoring of efficacy of LPLD gene therapy to support Phase I/II clinical trial design to be proposed to Health Canada at a pre-CTA meeting Definition and validation of the study population and of the main inclusion and exclusion criteria will be performed using data obtained from discussions with Canadian/international experts and from the documentation of the natural history of LPL deficiency, including epigenetic, gene expression and sequencing analyses. The natural history of LPL deficiency, including a panel of critical biomarkers, will become a ‘baseline’ against which to benchmark long-term efficacy of LPLD gene therapy. The analysis and selection of clinical biomarkers will leverage the ongoing research program on the natural history of severe hypertriglyceridemia (SMASH: Systems and Molecular Approaches of Severe Hyperlipidemias) (Table 1). In parallel, the same panel of biomarkers will be monitored in preclinical long-term safety and efficacy study of the lead LPLD gene therapy construct in LPL-/- transgenic mice conducted by UBC. This will provide pre-clinical baseline of potential effect of gene therapy treatment on selected biomarkers representative of the ‘natural’ history of disease in humans. ( Figure 1). Studies above will allow to identify safety and efficacy assessment criteria that will be used in the clinical trial, including the definition of the primary and secondary objectives, as well as to identify all potential concurrent and companion treatments. Finally, socioeconomic study of chylomicronemia and pharmacoeconomic analyses will be performed to position this new gene therapy in relation to the competitive environment and the burden of LPL deficiency