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ARCA Discovery Announces Data Demonstrating Potential for Bucindolol as Targeted Therapy in Heart Failure, Atrial Fibrillation, and Ventricular Arrhythmia
Date:11/6/2007

during the trial that examined the effects of bucindolol in beta-1 adrenergic receptor gene variants (beta-1 389 Arg/Arg and Gly carriers).

In the adrenergic receptor genetic substudy, chronic administration of bucindolol resulted in a significant reduction in cardiovascular hospitalizations and mortality. Effects on both were strikingly beta-1 389 Arg/Gly specific, with the higher functioning, Arg/Arg version of the receptor associated with large treatment effects (compared to placebo, reduction in time to event CV hospitalizations by 34% (p = 0.003), CV hospitalizations/patient by 35% (p = 0.005), number of days CV hospitalized/patient by 36% (p = 0.005), and cardiovascular mortality by 46% (p = 0.015)). The presentation concluded that genetic targeting of the beta-1 AR 389 polymorphism may improve the clinical responses to bucindolol for CV mortality and morbidity.

"Effect of b1 389 Arg/Gly a2c 322-325 Wt/Del Genotypes on Adjudicated Hospitalizations in the BEST Trial" (Presentation #2912) presented, in an oral presentation by Dr. Peter Carson of the Virginia Medical Center, data from a recent adjudication by the BEST nine member endpoints committee (EPC), in which they reviewed all 5,086 hospitalizations from the study, recognized by the FDA as an important endpoint in evaluating heart failure drugs.

The analysis revealed that the EPC method -- due to its level of specificity -- adjudicated fewer hospitalizations due to worsening heart failure as compared to the investigator/CRF method. In addition, the EPC adjudication tended to increase effect size, although the CRF method of identifying heart failure hospitalizations yielded similar qualitative results.

The results presented by Dr. Carson demonstrated both the beta-1 389 Arg/Arg adrenergic receptor polymorphism and the alpha-2c wild type gene variant are positively correlated with certain major clinical responses to bucindolol (all-cause mortality, cardiovascular mortality and days eac
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SOURCE ARCA Discovery, Inc.
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