The Silicon Review
“DalCor is currently conducting the dal-GenE study, a Phase-3 precision medicine outcomes trial to determine the efficacy of dalcetrapib in a genetically defined population with cardiovascular disease.”
Precision medicine is an integrative approach to disease prevention and treatment that considers an individual’s genetics, lifestyle, and exposures as determinants of their health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly.
Considering the foregoing, we are thrilled to present DalCor Pharmaceuticals who aim to develop precision treatments for cardiovascular disease by genetically targeting patients that will derive clinical benefits. By integrating clinical and genetic insights, DalCor intends to deliver superior clinical cardiovascular outcomes on top of standard of care treatment. The company’s development program, dalcetrapib, is intended to reduce cardiovascular events in a specific genetic subset of patients.
The company was incorporated in 2014 and has operations in Canada, the UK, Switzerland, and the U.S.
Dr Fouzia Laghrissi-Thode, DalCor Pharmaceuticals CEO, spoke exclusively to The Silicon Review. Below is an excerpt.
Q. Tell us about the development of dalcetrapib. What are the primary issues addressed by it? What are the various stages in the drug development process?
The development of dalcetrapib is a fascinating story. This drug is acting on cholesterol ester transfer protein (CETP) and was licensed by Roche from Japan Tobacco. Roche conducted a large development program called the dal-HEART program, which included a cardiovascular outcomes study dal-OUTCOMES conducted in 15,871 patients who had suffered an acute coronary syndrome (e.g., heart attack). However, the study was halted prematurely in 2012 due to futility, and while the drug was well-tolerated, there was no apparent cardiovascular outcomes benefit.
With the hypothesis that the response to dalcetrapib may vary according to the genetic background, a pharmacogenomic evaluation using a genome-wide approach in the dal-OUTCOMES study was then conducted in about 5,700 patients by the Montreal Heart Institute. Cardiovascular events were associated with the adenylate cyclase type 9 (ADCY9) gene on chromosome 16. Results also showed that patients had the AA genotype experienced a 39 percent reduction in the pre-specified composite endpoint of coronary heart disease (CHD) death, resuscitated cardiac arrest, non-fatal MI, non-fatal ischemic stroke, unstable angina, or unanticipated coronary revascularization with dalcetrapib compared with placebo.
With this new information in hand, Dalcor subsequently licensed the project from Roche. Further studies of the effect of dalcetrapib on inflammatory and cholesterol biomarkers such as high-sensitivity C-reactive protein and cholesterol efflux have also correlated with the benefits seen in the AA genotype patients. To confirm these findings, DalCor is currently conducting the dal-GenE study, a Phase-3 precision medicine cardiovascular outcomes trial to determine the efficacy of dalcetrapib in a genetically defined population. The trial has enrolled 6,149 post-acute coronary syndrome (ACS) patients who have the AA genotype at rs1967309 location in the ADCY9 gene. Results are anticipated in the first half of 2021.
Q. What are the notable functions of the precision medicine platform?
Despite current evidence-based therapies, the persistent cardiovascular risk following an ACS remains high, stressing the need for new targeted therapies. A pharmacogenomic strategy (based on the patient’s genetic profile) can help guide physicians with their treatment decision to achieve better outcomes for their patients — a concept that is already being applied in the field of oncology. Pharmacogenomic precision medicine is an emerging and exciting area for cardiovascular disease (CVD). We are delighted that DalCor is undertaking the first pharmacogenomic precision medicine cardiovascular (CV) outcomes trial dal-GenE, in post-ACS patients with the AA genotype in the ADCY9 gene.
Q. What are your trajectories for the next five years?
The focus of our work is on the clinical program and the read-out in the first half of 2021. While we believe there is significant value to patients and healthcare systems around the world, it is premature to comment on the commercial opportunity for dalcetrapib.
Dr Fouzia Laghrissi-Thode: A Dynamic Leader
Dr Fouzia Laghrissi-Thode became Chief Executive Officer of DalCor Pharmaceuticals in April 2018. Most recently, Dr Laghrissi-Thode was Vice-President, US Renal-Cardiology Therapeutic at AstraZeneca. In her previous roles, she led the global product and portfolio strategy of the cardiovascular, metabolism and renal therapeutic areas at AstraZeneca and Roche. She has more than 20 years of pharmaceutical industry leadership experience in the US and Europe through working in clinical development, global strategic marketing, business development, licensing, and M&A. She is a director on the board of Minerva Neurosciences Inc., Nuro Corp., and DalCor Pharmaceuticals. She served as a board member of the Healthcare Businesswomen’s Association (HBA) Europe and was recognized by HBA in 2012 for her work in developing and promoting women leadership in healthcare. From 1992 to 2014, she held an appointment as a faculty member at the University of Pittsburgh School of Medicine, UPMC, Western Psychiatric Institute, and Clinic. Dr Laghrissi-Thode is board certified in Psychiatry and holds Doctorate in Medicine from the University of Tours School of Medicine in France.