ARYx Therapeutics, Inc. Announces Successful Outcome of Atrial Fibrillation Clinical Trial on ATI-2042

ARYx Therapeutics, Inc. (NASDAQ: ARYX), a biopharmaceutical company, today announced successful top-line efficacy 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. By achieving statistical significance at the two highest doses of the three tested, the results essentially mirrored the findings of an earlier Phase 2 study also conducted in paroxysmal atrial fibrillation patients. Complete results from this study are expected in the first quarter of 2009.

“The results that we have analyzed to date from this study are excellent. Reported as a reduction in the percentage of time spent in atrial fibrillation compared to baseline, these results provide further evidence that ATI-2042 could be a highly effective agent in the treatment of atrial fibrillation,” said Dr. Paul Goddard, chairman and chief executive officer of ARYx.

“We believe we now have sufficient Phase 2 data to attract the right pharmaceutical company partner to continue the development of ATI-2042. 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 thought to be caused by its organ accumulation.”

Our Study Design

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. During the 12-week treatment period, each patient’s burden was measured and compared to their own baseline measurement. These results were then compared to the response in the placebo group.

By enrolling patients who had both paroxysmal atrial fibrillation and implanted recordable pacemakers, the data produced by this Phase 2b study provides an uninterrupted record of the patient’s atrial fibrillation burden, and other aspects of cardiac function, over a five-month period. In addition, the combination of this continuous recording capability of the pacemakers, linked to the study’s design, allows for a unique and robust set of data as compared to the data that have been typically available in prior anti-arrhythmic drug studies.

Our Study Results

The primary efficacy analysis was the percent change in the atrial fibrillation burden from baseline to the whole 12-week treatment period in the mITT¹ population. The primary statistical efficacy analysis² 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. Although the 200 mg BID dose decreased atrial fibrillation burden by 10%, this did not reach statistical significance. The overall dose response effect was both robust and linear with a p=0.0001. Randomization was balanced across all four treatment groups.

The primary efficacy analysis also included a month-by-month assessment of the patients’ burden. The reduction in atrial fibrillation burden was statistically significant in each of the 3 months of treatment in both the 400 mg BID group and the 600 mg BID group. The maximal effect of the drug was seen in the third month on 600 mg BID where the percentage reduction was 83% (p=0.009).

The benefit of ATI-2042 on the larger ITT³ population in reducing atrial fibrillation burden was also highly significant. The percentage reduction in atrial fibrillation burden for the 400 mg BID group was 54% (p=0.013) and for the 600 mg BID group it was 74% (p=0.001). Similarly marked dose response effect was seen (p<0.0001).

“It is really gratifying to see that as the dose and duration of treatment of ATI-2042 was increased, we see that the dramatic effect of the drug in reducing atrial fibrillation burden becomes even more pronounced,” explained Dr. Pascal Druzgala, senior vice president and chief scientific officer of ARYx.

While the detailed safety results have not yet been fully analyzed, it appears there were no drug-related serious adverse events and the drug appears to be well tolerated. The drop-out rate of patients from the study was minimal and balanced across all treatment arms. The complete analysis, expected by the end of the first quarter 2009, will cover a comprehensive safety and tolerability review as well as other secondary efficacy endpoints.

About the Patient Population in Our Study

The clinical characteristics of the patients enrolled in this Phase 2b trial were similar to those enrolled in other recent large scale trials, such as Canadian Trial of Atrial Fibrillation (CTAF), ADONIS, ERUDIS and ATHENA, testing other antiarrythmic drugs designed to treat atrial fibrillation. As such, we believe the results of this Phase 2b study compare favorably with the results of these other studies. These characteristics are also broadly representative of the general population of patients with atrial fibrillation.

On average, patients in our study had atrial fibrillation for 3 years before enrollment in the trial. Most of the patients had already failed other antiarrythmic drugs, 15% had been cardioverted and 17% had undergone atrial ablation procedures for treatment of atrial fibrillation. This appears to be a typical profile of the patient population of other atrial fibrillation trials when complete demographic information is disclosed from the study. The episodes of atrial fibrillation caused noticeable symptoms such as palpitations, shortness of breath, lightheadedness, fatigue and chest pain in most (71%) of the patients. The symptom severity was moderate, and 38% of the patients had been hospitalized one or more times for treatment of atrial fibrillation. Pacemakers were not implanted for the treatment of atrial fibrillation per se and did not influence the effect of treatment with ATI-2042. Coming into this study, the enrolled patients were in atrial fibrillation, on average, 26% of the time (AF burden), indicative of a significant risk factor for complications resulting from atrial fibrillation, particularly stroke.

About Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, or abnormal heart rhythm, affecting greater than 6.4 million people in the United States, Europe and Japan. It is estimated that atrial fibrillation is responsible for more than 75,000 strokes per year in the United States alone. AF affects about 5% of people older than 65