DeCode heart attack drug enters phase III

The trial, which will enroll 3400 patients with a history of recent heart attack, will focus on African-American heart patients who carry an at-risk variant of one of the genes DeCode has linked to risk of heart attack through the leukotriene pathway – the pathway targeted by DG031. The trial will also include patients without the at-risk variant.

The trial will evaluate a dose of 500mg of DG031 twice daily, and the primary endpoint is a composite of reduction in fatal and non-fatal heart attack and stroke, hospitalization for unstable angina, and the need for urgent revascularization.

DG031 is an inhibitor of 5-lipoxygenase activating protein, or FLAP. DeCode has linked variants in the gene encoding FLAP, and the gene encoding leukotriene A4 hydrolase (LTA4H) to risk of heart attack.

These variants appear to confer increased risk of heart attack by increasing the production of leukotriene B4 (LTB4), a potent driver of inflammation produced in atherosclerotic plaques. In phase II trials completed last year, DG031 was shown to be well tolerated at all doses tested and to reduce the production of LTB4 in a dose-dependent manner.

Late last year DeCode discovered that the HapK variant of the LTA4H gene, which confers a moderate increase in risk of heart attack in people of predominantly European ancestry, confers a 250% increase in risk of the disease in African Americans.

“In this trial we are using human genetics to take aim at the underlying biological causes of heart attack. Our approach enables us to conduct a highly sensitive study on a relatively small number of participants, focusing on a group at high identifiable risk through a pathway confirmed in many populations,” said Kari Stefansson, CEO of DeCode.

DeCode licensed DG031 from Bayer AG, which developed it originally for the treatment of asthma. In DeCode’s clinical trials and those conducted previously by Bayer, a total of approximately 2000 people have been dosed with DG031.