I believe ARYX afib data looks better than crme's
ARYx Therapeutics, Inc. Provides Additional Data on Atrial Fibrillation Clinical Trial on ATI-2042
Monday January 12, 7:00 am ET
Washout Data and Secondary End Points Reinforce Top-Line Efficacy
FREMONT, Calif.--(BUSINESS WIRE)--ARYx Therapeutics, Inc. (NASDAQ:ARYX - News), a biopharmaceutical company, today announced further results from a Phase 2b clinical trial testing the safety and efficacy of its oral anti-arrhythmic therapy, ATI-2042, in patients with atrial fibrillation. This follows the December 18, 2008 press release reporting that ATI-2042 reached statistical significance at its primary end point in the two highest of three doses tested. Those results are now reinforced by these additional findings indicating, in part, that patients in the study quickly returned to their pre-treatment level of atrial fibrillation once the treatment ended. The complete safety results from this study are still not finalized and are expected by the end of March 2009.
“These additional results broaden our confidence about the effectiveness of ATI-2042. We believe these incremental data provide additional clinical evidence that ATI-2042 does not accumulate in the body which is known to be a major liability with the treatment of choice, amiodarone,” stated Dr. Paul Goddard, chairman and chief executive officer of ARYx Therapeutics. “Our product has been designed to be as effective as amiodarone in a broad atrial fibrillation patient population, including those with congestive heart failure, but without its known safety problems. These additional Phase 2b results should support our efforts to find the right partner for the full development and eventual commercialization of ATI-2042.”
Our Study Design and Analyses
The clinical trial, which enrolled 72 patients, was a multi-centered, randomized, double blind, placebo-controlled study of the efficacy and safety of ATI-2042 in patients with paroxysmal atrial fibrillation (PAF). Patients entering this study all had previously implanted permanent pacemakers with appropriate diagnostic and recording capabilities. These devices were used to collect comprehensive cardiac data, including the percentage of time each patient spent in atrial fibrillation (their “burden”), as well as other aspects of cardiac function that will be incorporated in the complete results analysis. Patients were entered into a baseline screening period of up to 30 days during which their burden was measured to establish if they were eligible for the trial. Qualifying subjects were randomized to receive twice-a-day (BID) oral doses of 200 mg, 400 mg, or 600 mg ATI-2042, or placebo for a treatment period of 12 weeks. This treatment period was followed by a further 4-week observation period; the “washout period.” During this washout period, no new antiarrythmic drugs were permitted. Each patient’s burden during the 12-week treatment period was measured and compared to their own baseline measurement. These results were then compared to the response in the placebo group.
As previously announced, the primary statistical efficacy analysis showed significance for ATI-2042 at the 400 mg (p=0.015) and 600 mg (p=0.005) doses. The atrial fibrillation burden in these two treatment groups was reduced from baseline by 54% and 75%, respectively. Subsequent to the release of these top-line results, additional data have been generated.
Our Washout Period Results
Data related to the level of atrial fibrillation burden that existed in the treated patients during the 4-week washout period is now available. At the end of the washout period, pacemakers were interrogated and the atrial fibrillation burden data were analyzed in the same way as the active treatment data. In each of the three ATI-2042 dose groups, the atrial fibrillation burden returned to essentially their baseline values within the one-month washout period. The washout data show no evidence of accumulation or of a rebound effect in the atrial fibrillation burden.
Additional Indication of Lack of Drug Accumulation
In this study, we utilized slit-lamp examinations to measure whether crystal deposits, so-called microdeposits, were formed in the patients’ eyes as a result of treatment with ATI-2042. These microdeposits are thought to be an indication of whether drug accumulation occurs. For example, published studies have shown these corneal microdeposits appear in approximately 90% of patients treated with amiodarone for 3 months (HL Green, et al. JACC 1983;2:1114). While the safety data is still blinded, a review of the over-all results of the slit-lamp eye examinations conducted on patients in this Phase 2b study reveal that, after up to three months of treatment, 56 of 57 patients were free of corneal microdeposits. Along with the washout period data, these slit-lamp examination results provide evidence of the lack of tissue accumulation of ATI-2042 and its metabolites.
Our Secondary Endpoint Results
In addition to providing measurement of atrial fibrillation burden, the pacemakers used in this Phase 2b trial also provided study data on the secondary efficacy endpoints such as the duration of atrial fibrillation episodes and the total number of atrial fibrillation episodes. A significant benefit in terms of reductions in both the number and duration of atrial fibrillation episodes was demonstrated in the 600 mg BID dose group. Commensurate with the reduced duration of atrial fibrillation there was a significant increase in the duration of normal sinus rhythm. The goal of anti-arrhythmic therapies is to maintain patients in normal sinus rhythm. These improvements in the secondary endpoints were supportive of the primary endpoint, and provide a plausible biological explanation for the established dose-dependent reduction in atrial fibrillation burden seen in this trial’s top-line results. We believe these full efficacy results help explain how ATI-2042 will be of clinical benefit to patients with atrial fibrillation.
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