EP 263: Bringing the first cardiovascular gene editing therapy to patients with Sek Kathiresan

This week on The Genetics Podcast, Patrick is joined by Dr. Sek Kathiresan, CEO of Verve Therapeutics and SVP, Head of Obesity Research and Early Development at Eli Lilly. They discuss how protective genetic variants led to the development of a one-time gene editing therapy for heart disease in the face of early doubt, the phase one results for Verve-102, what recent trial failures mean for genetic target validation, and the unmet needs in obesity treatment. Show Notes 0:00 Intro to The Genetics Podcast 00:59 Welcome to Sek 01:41 Sek’s family history of heart disease and how it motivated him to pursue cardio therapeutics 03:45 Sek’s background and research on the genetics of coronary artery disease and protective mutations 08:32 Reactions to the Verve launch and the biological, technological, regulatory and commercial risks 11:39 Verve-102 phase one results and the case for lifelong LDL lowering 17:01 Why cumulative exposure means lowering LDL earlier and for longer 18:40 Recent trial failures in genetically validated targets and what the Lp(a) trial leaves unanswered 21:23 Polygenic risk scores and who benefits most from LDL lowering 24:31 Sek’s new role at Lilly and the remaining unmet needs in obesity treatment 30:17 Whether one-time gene therapy could work for obesity and how GLP-1 drugs drive weight loss 31:55 Food intake, energy expenditure, and the search for new obesity mechanisms 33:38 Why Lilly is investing so heavily in genetic medicine 36:03 Closing remarks Find out more: ANGPTL3 study in NEJM (https://pmc.ncbi.nlm.nih.gov/articles...) Verve-102 study (https://www.nejm.org/doi/10.1056/NEJM...)