ACCLAIM Phase III Trial

During 2006, we completed the 2,408-patient phase III ACCLAIM (Advanced Chronic Heart Failure CLinical Assessment of Immune Modulation Therapy) trial of Celacade in patients with chronic heart failure. This important study involved 175 clinical centers in seven countries and was designed to assess the ability of our Celacade technology to reduce the risk of death or first cardiovascular hospitalization. Dr. James B. Young, Chairman, Division of Medicine at The Cleveland Clinic Foundation and Medical Director, Kaufman Center for Heart Failure, acted as the Global Principal Investigator and Chairman of the Steering Committee for the ACCLAIM trial.

The ACCLAIM study included patients who had New York Heart Association (NYHA) Class II, III, or IV heart failure with a left-ventricular ejection fraction (LVEF) of 30% or less, and who had been hospitalized or received intravenous drug therapy for heart failure within the previous 12 months, or had NYHA Class III/IV heart failure with a LVEF of less than 25%.

Patients enrolled into the study were also receiving optimal standard-of-care therapy for heart failure, which included diuretics (94%), ACE-inhibitors or ARB (94%), beta blockers (87%), automatic implantable cardioverter defibrillators (26%), and cardiac resynchronization therapy (10.5%). The placebo (n=1,204 patients) and Celacade (n=1,204 patients) groups were well balanced for all important baseline characteristics, including demographics, LVEF, NYHA classification, concomitant medical conditions, medications, and device therapies.

In September 2006, Dr. Guillermo Torre-Amione, Medical Director, Heart Transplant Program, Methodist DeBakey Heart Center at The Methodist Hospital, and Principal Investigator for the U.S. arm of the ACCLAIM trial, presented the results from the study at the World Congress of Cardiology 2006 in Barcelona, Spain, and at the 10th Annual Scientific Meeting of the Heart Failure Society of America in Seattle, Washington. The difference in time to death or first cardiovascular hospitalization (the primary endpoint) for the intent-to-treat study population was not statistically significant (p=0.22); however, the risk reduction directionally favored the Celacade group (hazard ratio=0.92).

The key finding from ACCLAIM was in a pre-defined subgroup of 689 patients who had NYHA Class II heart failure at baseline. In this large subgroup of patients, Celacade was shown to reduce the risk of death or first cardiovascular hospitalization (the primary endpoint for the trial) by 39% (n=689 patients, 216 events, p=0.0003). Celacade was also shown to significantly reduce the risk of death or first cardiovascular hospitalization by 26% in a pre-defined subgroup of patients in NYHA Class II - IV with no prior history of heart attack (n=919 patients, 243 events, p=0.02).

The ACCLAIM trial also demonstrated that Celacade resulted in a significant improvement in quality of life (as measured by the Minnesota Living with Heart Failure Questionnaire) for the entire study population (n=2,408 patients, p=0.04). Consistent with earlier studies, Celacade was shown to be well tolerated in the ACCLAIM patient population; there were no significant between-group differences for any serious adverse events.

According to the Heart Failure Society of America, heart failure is the only major cardiovascular disease with prevalence and incidence on the rise. Heart failure, which is now often referred to as an epidemic, is estimated to affect 12 million individuals in North America and Europe, with an estimated 4.4 million having NYHA Class II stage disease. The financial burden of heart failure on the healthcare system in the United States alone is estimated to exceed $30 billion per year.

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