First ever clinical trial based upon the isolation of a disease gene in a common disease

deCODE Announces Positive Results from Phase IIa Clinical Trial of DG031

20-Oct-2004

deCODE genetics announced the principal results from its Phase IIa information-rich clinical trial" of DG031, the company's developmental compound which is being studied for the prevention of heart attack. The trial was designed to examine the effect of various doses of DG031 on certain biomarkers linked to arterial inflammation and risk of heart attack in patients with a history of heart attack and one or more of the gene variants deCODE has linked to increased risk of the disease. The company will host a conference call to discuss today's announcement. The call will be held at 3pm GMT/11am EDT today, Tuesday, October 19, 2004, and will be webcast live (details below).

Principal efficacy results

The trial achieved its primary efficacy endpoint of demonstrating a reduction in one or more of these key biomarkers. The results showed that at all dose levels DG031 suppressed production of leukotriene B4 (LTB4), the product of the branch of the leukotriene pathway that deCODE's genetics research has linked to increased risk of heart attack. At the highest dose level, DG031 reduced levels of myeloperoxidase (MPO), higher levels of which have been linked to increased risk of heart attack. These effects were dose-dependent. The study also demonstrated that at the highest dose, DG031 lowered levels of sICAM-I, a critical molecule in the activation of inflammatory cells and cell infiltration. There were no serious drug-related adverse events reported in this study, and DG031 was found to be well tolerated.

"Our population genetics work pointed us to the role of the leukotriene pathway and LTB4 in driving the inflammatory process underlying heart attack. DG031 is designed to inhibit the FLAP, or 5-lipoxygenase activating protein, which regulates the synthesis of leukotrienes. The results of this trial demonstrate that DG031 not only effectively supresses the synthesis of leukotriene B4, but at the same time also reduces levels of myeloperoxidase, another marker correlated with cardiovascular risk," said Dr. Kari Stefansson, CEO of deCODE. "The finding that MPO levels correlate with those of LTB4 suggests that MPO may serve as a surrogate for risk of heart attack through the pathway targeted by DG031. We believe this finding will assist us in designing the next phase of clinical development, in which DG031 will be studied for the prevention of heart attack."

DG031 is a small-molecule FLAP-inhibitor originally developed by Bayer AG. deCODE acquired worldwide development rights to DG031 from Bayer in November 2003, and Bayer's IND for the compound was transferred to deCODE.

https://www.bionity.com/en/news/40363/first-ever-clinical-trial-based-upon-the-isolation-of-a-disease-gene-in-a-common-disease.html