Cardiome Pharma Corporation posted positive interim clinical results from its 90-day phase IIb study of vernakalant (oral). The interim analysis demonstrated statistically significant efficacy for the patient group receiving 500mg b.i.d. of vernakalant (oral) as compared to placebo. The safety data from the interim analysis also suggests that vernakalant (oral) was well-tolerated in the atrial fibrillation population studied during the dosing period under analysis.
A Kaplan-Meier analysis of the 446 patients included in the interim dataset demonstrated a significant efficacy benefit for the 500mg dosing group as compared to placebo (two-sided, p<0.05). Median time to recurrence of atrial fibrillation was greater than 90 days for the 500mg dosing group, compared to 39 days for the placebo group. 52 per cent of patients in the 500mg dosing group (n=110) completed the study in normal heart rhythm compared to 39 per cent of patients receiving placebo (n=118). The interim efficacy analysis for the 150mg (n=110) and 300mg (n=108) dosing groups had not achieved statistical significance at the interim timepoint.
"This larger-scale, longer-term study of vernakalant (oral) was designed to find the appropriate dose to take into phase III, and to confirm our assumptions regarding safety," said Dr. Charles Fisher, executive vice president and chief medical officer, Cardiome. "While the study is ongoing and we must await the final data before drawing conclusions, these statistically significant and clinically significant efficacy results as well as the attractive safety profile observed in this interim analysis strongly support our belief in the exciting potential of vernakalant (oral) as a therapy for atrial fibrillation."
The safety data for all dosing groups suggests that vernakalant (oral) was well-tolerated within the interim safety population (n=537), which includes patients randomised who did not enter the maintenance phase of the study. During the dosing period under analysis, there was no difference in the incidence of serious adverse events between treatment groups. Potentially drug-related serious adverse events occurred in 1 per cent of placebo patients, 2 per cent of patients in the 150mg dosing group, 0 per cent of patients in the 300mg dosing group and 1 per cent of patients in the 500mg dosing group. There were no cases of drug-related "Torsades de Pointes", a well-characterised arrhythmia which is an occasional side effect of some current anti-arrhythmic drugs. There were 2 deaths during this period, both unrelated to vernakalant (oral), comprising a patient in the 150mg dosing group who died of cervical cancer at day 79, and a patient in the placebo group who died at day 86 after suffering an ischemic stroke.
"Our strategic intent with this study was to pave the way to phase III and provide efficacy and safety data to support business discussions," said Bob Rieder, chairman and chief executive officer, Cardiome. "This strong interim data set clearly enables us to move forward in planning the phase III programme and continue our discussions with interested parties."
The double-blind, placebo-controlled, randomized, dose-ranging study was designed to explore safety and tolerability, pharmacokinetics and efficacy of vernakalant (oral) over 90 days of dosing in patients at risk of recurrent atrial fibrillation. Patients received a 150mg, 300mg or 500mg dose of vernakalant (oral) or placebo twice per day. After the first 3 days, patients still in atrial fibrillation were electrically cardioverted. Successfully cardioverted patients continued to receive vernakalant (oral) or placebo for the remainder of the 90-day trial and were monitored throughout the dosing period.
Cardiome initiated the phase IIb in the first quarter of 2007. Enrolment has completed, with a total of 735 patients randomised, of which approximately 590 patients are expected to enter the maintenance phase and be measured for efficacy. Final results from the study are expected in the third quarter of 2008.
Cardiome also announced that it has received detailed expressions of interest from global and regional pharmaceutical companies in pursuit of partnership opportunities for vernakalant. Cardiome's Board of Directors has engaged Merrill Lynch & Co. as its financial advisor to assist in evaluating these partnership opportunities as well as alternative strategies beyond partnerships to maximise shareholder value, including acquisitions, divestitures and the sale of all or part of the company.
"We began a partnership cycle in the second half of 2007 in anticipation of the US approval of vernakalant (iv) and results from the vernakalant (oral) Phase IIb trial," said Doug Janzen, President and Chief Business Officer of Cardiome. "In light of today's positive results, we look forward to furthering our partnership discussions with those companies who have expressed interest to date, and welcome Merrill Lynch's assistance in ensuring shareholder value is maximized. Obviously, there can be no assurance that Cardiome's review of partnership opportunities and other strategic alternatives will result in any specific transaction, and while this review is about to be initiated, no timetable has been set for its completion."