deCODE genetics announced that it has begun enrolling patients for its phase IIa clinical trial for DG051, the company's leukotriene A4 hydrolase inhibitor being developed for the prevention of heart attack.
In phase I studies completed earlier this year, DG051 significantly reduced the production of leukotriene B4 (LTB4) in a dose dependent manner. LTB4 is a pro-inflammatory molecule that deCODE's gene discovery and functional biology work identified as a key factor in modulating risk of heart attack. The phase I studies showed DG051 to be safe and well-tolerated at all dose levels tested, with a favourable pharmacokinetic profile. DG051 was also recently evaluated in a 28-day phase I study that further demonstrated that the drug could deliver significant, sustained reductions in LTB4 levels with once-daily dosing, said a company press release.
The design of the phase IIa study is based upon these findings by studying the effect of DG051 in patients with a history of heart attack or coronary artery disease. The Phase IIa is a randomised, double-blind, placebo-controlled trial that will examine the impact of DG051 on the production of LTB4 as well as the compound's pharmacokinetic and safety and tolerability profiles in heart patients. The company will use the results from this study to inform dose selection for a larger phase IIb trial planned to commence early next year.
"We are advancing DG051 as a novel means of preventing heart attack, the leading cause of death in the industrialized world. Our clinical studies thus far have shown that it effectively reins in the activity of a branch of the leukotriene pathway that has been linked to risk of heart attack, and it has demonstrated a solid safety and pharmacokinetic profile. The 28-day study we just completed shows that DG051 can achieve good reductions in leukotriene B4 levels with once-daily dosing. We are excited to have begun testing its potential in patients," said, Kari Stefansson, CEO, deCODE.
DG051 is a first-in-class, small-molecule inhibitor of leukotriene A4 hydrolase (LTA4H) discovered by deCODE's chemistry unit and is being developed for the prevention of heart attack. LTA4H is encoded by one of the genes deCODE has linked to increased risk of heart attack. The at-risk versions of these genes confer increased risk of heart attack by increasing the production of the pro-inflammatory molecule LTB4. DG051 is designed to decrease risk of heart attack by decreasing the production of LTB4, the company statement said.
deCODE genetics is a global leader in applying human genetics to develop drugs and diagnostics for common diseases. Our population approach has enabled us to discover and target key biological pathways involved in conditions ranging from heart attack to cancer. We are turning these discoveries into new medicine to better treat and prevent many of the biggest challenges to public health