Reykjavik, ICELAND, May 10, 2005 – deCODE genetics (Nasdaq:DCGN) today announced the publication of a landmark article by a team of its scientists presenting the results of Phase II clinical studies of DG031, the company’s lead compound being developed for the prevention of myocardial infarction, or heart attack. The results demonstrate that DG031 works to correct a biological perturbation caused by genetic risk factors for heart attack the company has identified, and lowers levels of well established biomarkers for risk of heart attack, including C-reactive protein (CRP) and myeloperoxidase (MPO). The article, entitled “Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial,” is published today in the online edition of the Journal of the American Medical Association (JAMA) at www.jama.com, and will appear in tomorrow’s print edition of the journal.
“This is a pioneering demonstration of how human genetics is pointing the way to potentially powerful new medicine. Our gene discoveries have given us novel insights into the biology of heart attack, the biggest killer in the industrialized world. The at-risk versions of the FLAP gene up-regulate the production of an important inflammatory mediator, leukotriene B4 (LTB4), increasing the propensity of atherosclerotic plaques will rupture, causing heart attack. The results of our Phase II clinical work with DG031 show that it can, by inhibiting FLAP, effectively reduce the production of LTB4 in a dose-dependent manner,” said Kari Stefansson, CEO of deCODE. “The same biological pathway is also up-regulated in some heart attack patients who do not have the at-risk gene variants we have found, suggesting that it may also capture important environmental risk. The effect of DG031 on CRP and myeloperoxidase, which come on top of the effects of statin therapy, is further evidence that we are effectively targeting a major biological mechanism contributing to heart attack. The next step in the development of DG031 is a Phase III clinical trial to directly examine its effectiveness in preventing heart attack.”
DG031 is a small-molecule inhibitor of the 5-lipoxygenase activating protein, or FLAP, encoded by a gene that deCODE has linked to significantly increased risk of heart attack. deCODE has also isolated a second gene in the leukotriene pathway, the gene encoding the leukotriene A4 hydrolase (LTA4H), that is directly involved in the synthesis of LTB4 and is also linked to risk of heart attack.
The primary goal of the Phase IIa clinical trial, the results of which are presented in the study published today, was to examine whether DG031 could reduce levels of LTB4 and other biomarkers of risk of heart attack in patients with the at-risk versions of either of these two genes. The results of the Phase IIa trial, which was completed last fall, showed that in subjects receiving a dose of 750mg/day, DG031 reduced LTB4 levels by 26% and myeloperoxidase levels by 12%. CRP levels were reduced in the groups receiving the 500mg and 750mg/day doses in the first 4 week dosing period, although this reduction became more pronounced and reached a significant 25% two weeks after the end of the dosing period. In early 2005, deCODE conducted a 75-patient, 8-day open-label follow-on study to further examine the effect of DG031 on CRP and myeloperoxidase. In this study, CRP levels were significantly reduced by 23% for all subjects, with a significant reduction of 38% for those receiving 250mg three times a day. Six hours after dosing on day 8, myeloperoxidase levels were reduced for the entire group by 20%, and by 31% in those receiving 250mg three times a day.
Trial design and patient profile
The double-blind, variable-dose, placebo-controlled, crossover Phase IIa study was conducted in Iceland with 172 participants completing the trial. Subjects were individuals who had a history of heart attack and/or coronary artery disease and who carry one or more of the at-risk gene variants deCODE has linked to heart attack. In the first four weeks of the trial, half the subjects received DG031 at one of three different dose levels – 250mg tablets once, twice or three times daily – and half received placebo. After a two-week washout period, the original placebo group received DG031 for four weeks according to the same dose schedule, and the other group received placebo. The follow-up study enrolled 75 patients according to the same criteria as the Phase IIa trial, divided into three groups of 25 subjects each. One group received one dose of 375mg/day, and two received 750mg/day, either as two doses of 375mg, or three doses of 250mg.
Safety and tolerability results
DG031 was well-tolerated and there were no serious drug-related adverse events in either clinical study. There was no significant difference in liver function tests between patients on drug and on placebo. The most common adverse event was mild dizziness, reported by six subjects on active drug, but which did not interfere with the daily activities of these patients.
About deCODE genetics
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs for common diseases. deCODE is a global leader in gene discovery — our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODE’s filings with the Securities and Exchange Commission. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.