AtheroGenics Inc announced that data presented at the American Heart Association (AHA) 2001 Scientific Sessions confirm that its lead compound, AGI-1067 met its primary endpoint in preventing restenosis in a Phase II clinical trial for post-angioplasty patients. Results from CART-1 (Canadian Antioxidant Restenosis Trial) were presented by principal investigator, Jean-Claude Tardif, of the Montreal Heart Institute.

Dr. Tardif also presented additional analyses that suggested, in addition to preventing post-angioplasty restenosis, AGI-1067 had a direct anti-atherosclerotic effect on coronary blood vessels, consistent with reversing the progression of coronary artery disease. AtheroGenics will initiate a major clinical trial next month to study prospectively this direct effect on atherosclerosis.

CART-1 was a 305-patient clinical trial that compared three doses of AGI-1067 (70 mg, 140 mg and 280 mg), given for six weeks, to placebo and probucol, a drug that has been shown to prevent restenosis. The primary endpoint of the trial was the size of the luminal area (coronary artery opening), as measured by intravascular ultrasound (IVUS), six months after angioplasty. CART-1 results showed that the study met its primary endpoint, with mean minimal luminal areas of: 2.66 mm2 (placebo); 3.69 mm2 (probucol); 2.75 mm2 (70 mg), 3.17 mm2 (140 mg) and 3.36 mm2 (280 mg) (p<0.05 for both the AGI-1067 dose response and for 280 mg AGI-1067 vs. placebo).

Angiographic restenosis was also assessed using a standard definition of restenosis as measured by quantitative coronary angiography (QCA). Rates of angiographic restenosis in stented arteries were 37.5 per cent for placebo, 25.5 per cent for probucol, and 26.0 per cent in the combined AGI-1067 arms. This yielded a restenosis rate reduction of 32 per cent and 31 per cent by probucol and AGI-1067, respectively.

An early direct benefit on coronary artery disease was evident at two weeks as shown by a dose response improvement (p<0.05) of the luminal area at the site of angioplasty for patients who received AGI-1067. This direct benefit was maintained at the angioplasty site at the six-month follow-up, as measured by repeat angiography.

Dr. Tardif also reported striking new data, consistent with a direct effect on atherosclerosis progression, from a recent post-study IVUS analysis of vessels that were not targets of angioplasty procedures. In this analysis, lumen volumes in reference blood vessels of coronary arteries decreased for patients on placebo, consistent with the expected progression of atherosclerosis. In contrast, patients who received either of the top two doses of AGI-1067 had increased lumen volumes. These lumen volume changes were measured as: -5.3 mm3 for placebo, -0.2 mm3 for probucol, -2.4 mm3 for AGI-1067 70 mg, +3.5 mm3 for AGI-1067 140 mg, and +1.8 mm3 for AGI-1067 280 mg.

"In CART-1, AGI-1067 demonstrated its effectiveness in reducing the incidence and severity of restenosis after only six weeks of dosing," said Dr. Tardif. "In addition, the drug appeared safe and well tolerated by the patients in this study at all doses. The early benefit appears to be an anti-atherosclerosis effect that improved the overall success rate of angioplasty and achieved a better result acutely. Perhaps most exciting is the IVUS analysis we have just completed, which suggests that AGI-1067 may also be reversing the progression of coronary disease. I am delighted that AtheroGenics will initiate clinical trials to address this question prospectively."

The Company is expediting clinical development of AGI-1067 with subsequent Phase II trials, the first to be initiated in December 2001, to study the effect of AGI-1067 on restenosis after ad hoc angioplasty procedures and in patients with type 2 diabetes.