Washington Editor

Positive Phase IIa data boosted shares in Cardiome Pharma Corp. as investors reacted favorably to interim findings on an oral atrial fibrillation drug.

On Monday, the Vancouver, British Columbia company's stock (NASDAQ:CRME) gained $3.24, or 36.4 percent, to close at $12.15. The drug, RSD1235, is being investigated as a chronic-use treatment for the maintenance of normal heart rhythm following termination of atrial fibrillation.

Specific data revealed that a 300 mg dose of oral RSD1235 has produced a positive trend toward efficacy so far, with 61 percent of patients on it completing the pilot study with normal heart rhythm as compared to 37 percent of those on placebo. Those findings, Cardiome CEO Bob Rieder said in a conference call, represent "tangible, real evidence of efficacy."

While the study was not sized for statistical significance, Doug Janzen, the company's president and chief business officer, noted only half the placebo patients have been included in this analysis. That means final results could look even better. "To see such a clear signal off this interim look," he said in the conference call, "has us very excited."

The good data stand in contrast to recent news that the FDA had refused to review a new drug application for intravenous RSD1235. That revelation caused Cardiome's shares to drop 20 percent to $9.03, even though the agency did not refer to inadequacies in the data package. Instead, Rieder labeled the problem "an execution error." (See BioWorld Today, June 1, 2006.)

The submission was based on a five-year clinical program and included data from two pivotal trials. Results from one of them showed that intravenous RSD1235 converted 52 percent of patients with recent onset atrial fibrillation to normal heart rhythm compared to 4 percent in the placebo group, and data from the other trial were nearly identical. That version of the product is being positioned as a means of bringing patients out of atrial fibrillation, an alternate to electric shock devices, with a market potential of about $500 million. (See BioWorld Today, April 3, 2006.)

The intravenous formulation is partnered with Astellas Pharma US Inc., a Deerfield, Ill.-based subsidiary of Astellas Pharma Inc. in Tokyo. An amended application is expected later this year, possibly at the end of this quarter but more likely in the early part of next quarter.

Cardiome has worldwide rights to oral RSD1235, which would enter a market estimated at about $1.5 billion.

Its double-blinded, randomized study has explored that formulation's safety and tolerability, pharmacokinetics and preliminary efficacy over 28 days of dosing in patients at risk of recurrent atrial fibrillation. Most of those enrolled in the trial had experienced atrial fibrillation for more than 30 days but less than 180 days in duration.

"That hopefully will delay the onset of their next attack," said Don Graham, Cardiome's director of corporate communication, adding that "there's really no effective treatment" that prevents patients from recurrent atrial fibrillation.

Patients in the first stage of the study received a 300 mg dose of oral RSD1235 or placebo twice per day. After the first three days, those still in atrial fibrillation were electrically cardioverted. A total of 83 patients were successfully cardioverted after the initial three days of dosing, after which they continued to receive oral RSD1235 or placebo for 25 more days. Of them, 81 reached an endpoint: completion of dosing or relapse to atrial fibrillation.

The other patients were discontinued for reasons unrelated to atrial fibrillation.

Further data showed the product to be well tolerated to date. During the 28 days of dosing, serious adverse events occurred in 10 percent of oral RSD1235 patients and 9 percent of those on placebo. Potentially drug-related serious adverse events occurred in 4 percent of patients receiving the study drug and 3 percent of placebo patients. There were no cases of drug-related Torsades de Pointes, a well-characterized arrhythmia that is an occasional side effect of some current anti-arrhythmic drugs.

Enrollment and dosing for the study's second stage, evaluating patients on a 600 mg dose of oral RSD1235 or placebo twice per day, also has been completed. Results from this group, as well as complete study findings, are expected later this quarter.

The trial, which Cardiome began in December, was conducted in the U.S., Canada and Europe. Graham declined to comment on the potential design of a larger Phase IIb study of oral RSD1235, which will follow analysis of the final results.