AstraZeneca has formed collaborations with the Montreal Heart Institute (MHI) in Quebec, Canada, to search the genomes of up to 80,000 patients for genes associated with cardiovascular diseases and diabetes, their complications and treatment outcomes, and with Abbott to develop companion diagnostic tests to identify patients with severe asthma who are most likely to benefit from the investigational biological therapy tralokinumab.

MHI will genotype up to 80,000 DNA samples from AZ’s extensive biobank. The samples include both tissue and blood samples, which have been collected over 12 years under informed consent from patients who have entered clinical trials to test cardiovascular or diabetes treatments.

MHI’s Beaulieu-Saucier Pharmacogenomics Center initially will use an approach called genome-wide SNP analysis to identify regions of DNA that predispose to, or cause, cardiovascular diseases and diabetes or are associated with responses to treatments. They will then apply other technologies, such as next-generation sequencing, to carry out full gene sequencing of areas of interest to identify new genes associated with disease, with complications such as heart attacks, strokes, diabetic nephropathy or retinopathy, and with treatment outcomes in terms of responsiveness to medication.

The knowledge gained from genotyping the samples will be applied to the development of new medicines tailored to treat subsets of patients with particular genetic profiles. The information also will enable a personalized healthcare approach to the use of existing treatments, which means using specific medicines to treat the patient populations that are most likely to respond. Currently, approximately 80% of AZ’s pipeline benefits from a personalized healthcare approach.

Dr. Jean-Claude Tardif, director of the Montreal Heart Institute Research Center and holder of both the Canada research chair in personalized and translational medicine and the Université de Montréal endowed research chair in atherosclerosis, said, “This large-scale partnership between AZ and the Montreal Heart Institute holds great potential for breakthroughs in personalized cardiovascular medicine and diabetes whereby medications will be tailored to responsive patients based on their genetic profile.”

According to its “open innovation” approach to R&D, AZ will work with MHI to publish findings in peer-reviewed journals, contributing to broader scientific understanding of these disease conditions.

AZ’s second agreement with Abbott focuses on developing companion diagnostic tests for severe asthma. To date, no companion diagnostic blood tests have been approved for use in asthma. Abbott will develop and commercialize diagnostic tests to measure serum levels of the proteins periostin and DPP4 (dipeptidyl peptidase-4), which have been identified as potential predictive biomarkers of up-regulated IL-13 in severe asthma. The tests will be developed in conjunction with AZ’s phase III trial of tralokinumab, a potential treatment for patients with severe, inadequately controlled asthma, developed by the company’s biologics R&D arm, MedImmune. Periostin previously has been described as a potential biomarker for asthma1, and DPP4 is a novel and promising predictive biomarker identified by MedImmune.

The tralokinumab phase III program will evaluate the safety and effectiveness of tralokinumab in reducing the rate of asthma exacerbations in adults and adolescents with severe, inadequately controlled asthma despite receiving inhaled corticosteroids plus long-acting β2-agonist. The program also will assess the effect of tralokinumab on lung function, patient-reported asthma symptoms and quality of life, as well as investigate whether serum periostin or DPP4 could identify patients who are most likely to benefit from tralokinumab.

Bing Yao, senior vice president and head of MedImmune’s respiratory, inflammation and autoimmunity innovative medicines unit, said, “This partnership with Abbott to develop companion diagnostics for tralokinumab is an important step in delivering on our ambition to bring innovative options for patients who continue to suffer with severe asthma. We anticipate that physicians ultimately will use these tests to better identify patients likely to benefit most from tralokinumab to bring their condition under control. We are on the cusp of a new era in personalized healthcare, one which will see great improvements for patients treated with respiratory medicines.”

Personalized healthcare is at the center of AZ’s approach to drug discovery and development and this collaboration is part of the company’s strategy to seek external partners to develop companion diagnostics that will help transform patients’ lives.