Positive data from ACT 1, a pivotal trial of Astellas/Cardiome's Kynapid (vernakalant injection) to treat atrial fibrillation, were published in the March 25 issue of Circulation, the American Heart Association journal.

An FDA decision on an NDA for the injection formulation of the potassium and sodium channel blocker was due Jan. 19, but has been delayed. FDA's Cardiovascular and Renal Drugs Advisory Committee voted last December that the NDA should be approved (¹ Also see "Astellas/Cardiome’s Vernakalant Wins Advisory Committee Approval In 6-2 Vote" - Pink Sheet, 11 December, 2007.).

Bruce McNutt, Astellas Pharma US senior medical director, told "The Pink Sheet" DAILY his company is eager for a decision, especially since it believes it has provided data sufficient for approval. Astellas previously reported positive data from the Phase III ACT 3 trial.

"We think that the data speaks for itself," McNutt said. "But we're going to do anything we can to help the FDA have enough information if that's the hold-up; we just don't know exactly what the problem is."

ACT 1 was a randomized, double-blind, placebo-controlled Phase III trial assessing 220 patients with symptomatic atrial fibrillation or nontypical atrial flutter at 44 sites in the U.S., Canada and Scandinavia. The primary efficacy measure was the percentage of short-duration (three hours to seven days) patients converted to sinus rhythm for at least one minute within 90 minutes of start of treatment.

In the short-duration group, 51.7 percent of patients - 75 out of 145 - converted to sinus rhythm within 90 minutes of the start of treatment, compared with 4 percent (three out of 75) of patients in the placebo group. In patients with AF lasting between three and 48 hours, 62.1 percent of treatment arm patients converted, compared with 4.9 percent in the control arm.

"The other takeaway is that those people who did convert, converted fairly quickly at 11 minutes on average from the time the infusion started," McNutt said. Since infusion lasted 10 minutes, this meant conversion occurred within a minute of initial treatment being completed. Patients not converted after 15 minutes were given a second 10-minute infusion.

McNutt also noted that while the primary endpoint called for conversion to last one minute, the patients were tracked for 24 hours and only one of the 75 responsive patients in the treatment arm relapsed to atrial fibrillation during that period. "The difference compared to placebo was quite dramatic," he said.

Kynapid also demonstrated safety in the ACT 1 trial, as ventricular arrhythmia occurred at the same rate in the treatment and placebo arms, McNutt said. There were four serious adverse events possibly or probably related to Kynapid, Astellas reported. The most common AEs were taste disturbance (29.9 percent) and sneezing (16.3 percent).

McNutt said if the drug wins FDA approval, Astellas likely will market it to cardiologists, emergency room and intensive care physicians, and cardiothoracic surgeons, particularly those who perform coronary bypass and cardiac valve surgeries. Astellas also is running a study to test the drug's benefit in surgical patients, he added, with initially promising findings.

Earlier this month, Cardiome reported positive Phase IIb data for an oral formulation of vernakalant (² Also see "Cardiome Reports Positive Oral Vernakalant Data; Says Company Sale Is Possible" - Pink Sheet, 17 March, 2008.). Cardiome discovered the compound and partnered with Astellas, with the latter assuming 75 percent of the development costs for the IV formulation in exchange for full North American commercialization rights.

-Joseph Haas (j.haas@elsevier.com)

Astellas/Cardiome Reports Positive Kynapid Phase III Study

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