Principal Investigator: Dr Paul McGettigan
Department: Novartis Ireland Limited
Dr Kristijan Kahler, Novartis Pharma AG, Basel, SwitzerlandTags: 59456, Drug development, Drug target, epidemiology, patient stratification, PheWAS, target-discovery
Novartis’ goal is to develop innovative medicines across the entire range of human disease. Drug development is very challenging: it takes a long time and has a high failure rate. This failure rate can be reduced by utilizing genetic information to make better choices about which patients and which diseases are targeted by a drug. We wish to use the combined genetic data and patient phenotype data available in the UK Biobank to: inform our drug development strategy, identify new drug targets and better characterize patient populations so that the drug programs we pursue are targeted at the patients who will benefit most.
The initial projects will focus on several heart related diseases i.e. hypercholesterolaemia and hyperlipoproteinaemia. Novartis has active drug programs targeting specific genetic targets of these conditions i.e. a siRNA therapy to lower LDL-C (inclisiran) and an Lp(a) antisense inhibitor (pelacarsen). There is a need to understand the epidemiology and phenotypic characteristics of patients who are at high risk of suffering from cardiovascular events but who could benefit from these classes of therapies.
The initial project will aim to determine predictors of cardiovascular risk and mortality in patients with elevated LDL-C and/or elevated Lp(a) levels. The project will involve characterizing the participants who have evidence of atherosclerotic cardiovascular diseases including their current treatment patterns and health outcomes.
We will look at the subjects who have high risk genotypes and a history of prior cardiovascular (CV) events and determine if there are demographic, environmental or additional genetic variables that discriminate between this population and those participants who have no equivalent history of CV events.
The results of these projects will be used, as input into clinical trials and presented as talks or posters at the relevant international cardiovascular conferences and/or published in peer reviewed cardiovascular journals.
This research will help to determine which patients will benefit most from these targeted therapies. This information can then be used to inform the population level strategy for reducing heart disease in the UK (where it is currently the second biggest cause of death).