Nearly seven months after the early closeout of the pivotal Phase III study of Celacade in peripheral arterial disease, Vasogen Inc. reported that the product missed its primary endpoint in improving patients’ walking distance over placebo.

Results, presented Sunday in a late-breaking session at the American College of Cardiology meeting in Atlanta, failed to show a statistically significant difference between the Celacade and placebo groups in maximal treadmill walking distance at 26 weeks. There also was no statistical difference between the groups in pain-free treadmill walking distance.

Shares of Vasogen (NASDAQ:VSGN) lost 73 cents, or 24.1 percent Monday, closing at $2.30.

However, the Toronto-based company said it is encouraged by the overall anti-inflammatory effect produced by the Celacade technology and is hoping to see that same effect from the larger Phase III trial in chronic heart failure patients. Results from that trial are expected during the first half of this year.

Data from the 553-patient SIMPADICO (Study of Immune Modulation Therapy in Peripheral Arterial Disease and Intermittent Claudication Outcomes) trial show "a number of supportive findings," Vasogen President and CEO David Elsley said during a conference call, and "we believe the implications are far-reaching" for cardiovascular indications.

The SIMPADICO results were not unexpected, particularly after the external safety and efficacy monitoring committee recommended closing out the trial in August, citing the lack of an efficacy signal based on data available at the time. That news caused Vasogen’s stock to plummet 44 percent to close at $2.38. (See BioWorld Today, Aug. 31, 2005.)

"While we’re disappointed by [the results], our disappointment is tempered by the knowledge that this is one of the most difficult endpoints in which to show a benefit," and that other analyses of the data indicated positive trends, said Eldon Smith, vice president of scientific affairs.

"There was evidence of a robust anti-inflammatory effect, on top of anti-inflammatory drugs," he added.

Patients treated with the Celacade technology showed a marked reduction in high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation associated with the increased cardiovascular risk that leads to heart failure, stroke and heart attack. Mean hs-CRP was reduced by 0.93 mg/L in the Celacade group, compared to an increase of 0.50 mg/L for placebo. A majority of patients in both groups also were taking anti-platelet therapy, usually aspirin, and lipid-lowering therapy, usually statins.

"By the end of the study, levels were reduced in the Celacade group by 20 percent, and increased by 13 percent in the placebo group," Smith said. "That is statistically significant."

He added that hs-CRP is believed to be a reliable marker of atherosclerosis, independent of cholesterol levels, and potentially is as important in predicting heart failure.

In addition to hs-CRP reduction, patients in the Celacade group also experienced a decrease over placebo in PAD-related and cardiovascular outcome events, with the biggest decrease seen in progression to critical limb ischemia (CLI), with three patients in the Celacade-treated group experiencing CLI, vs. 12 in the placebo group.

Changes in life quality and ankle-brachial index did not reach significance, but Celacade demonstrated positive trends in the areas of physical functioning, social functioning, walking impairment and distance. The product was found to be well tolerated in the patient population, which consisted primarily of men (72 percent), with an average age of 67. About 91 percent of the patients were current or ex-smokers.

Overall, Smith called the results "interesting and encouraging," and said that "if we see the same sort of data in the ACCLAIM trial, that should translate in a very significant reduction in events."

The 2,400-patient ACCLAIM (Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy) study has finished enrollment and treatment, and researchers are in the process of collecting data to begin analysis. The trial is designed to assess the use of the Celacade technology in reducing the risk of death and hospitalization in heart failure patients.

"We plan to lock the data in May, and will report results shortly after that," Smith said.

Vasogen still is in partnership discussions for Celacade, a technology designed to deliver oxidative stress to a sample of the patient’s own cells. During a monthly outpatient procedure, a blood sample is collected using a disposable cartridge and then exposed to oxidative stress before being re-administered through an intramuscular injection.

Behind Celacade, the company has a neuro-inflammatory program, led by VP025, which is set to begin a Phase IIa study in the second half of this year.

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