Merck and Cardiome Pharma announced that the intravenous (IV) formulation of vernakalant (Brinavess) has been granted marketing approval in the European Union (EU), Iceland and Norway for the rapid conversion of recent onset atrial fibrillation (AF) to sinus rhythm in adults: for non-surgery patients with AF of seven days or less and for post-cardiac surgery patients with AF of three days or less.
Vernakalant acts preferentially in the atria and is the first product in a new class of pharmacologic agents for cardioversion of AF to launch in the EU.
“This medicine offers physicians, patients and hospitals an important new therapy option to use for the rapid treatment of recent-onset AF,” said Patrick Magri, senior vice president, general manager, Cardiovascular Franchise, Merck.
“European approval of vernakalant and Merck’s subsequent launch represent an exciting juncture in Cardiome’s evolution which will provide us with our first commercial product revenues,” said Doug Janzen, president and chief executive officer of Cardiome.
The approval of vernakalant is based on the results of three randomised, double-blind, placebo controlled studies (ACT I, ACT II, and ACT III) and an active comparator trial (AVRO).
In ACT I and III, the efficacy of vernakalant at converting patients from AF to sinus rhythm for a minimum duration of one minute with 90 minutes of initiating therapy was evaluated in 390 haemodynamically stable adult patients with short duration AF (3 hours to 7 days) vs. placebo. In ACT I, vernakalant cardioverted 51.0% of patients vs. 4.0% of patients taking placebo (n=74 and 3, respectively; p<0.0001). In ACT III, vernakalant cardioverted 51.2% of patients vs. 3.6% of patients taking placebo (n=44 and 3, respectively; p<0.0001). Conversion of AF to sinus rhythm occurred rapidly; in responders, the median time to conversion was 10 minutes from start of first infusion, based on pooled results from the ACT I and ACT III studies.
The efficacy of vernakalant was also studied in ACT II in 150 patients with sustained AF (3 hours to 72 hours duration) that occurred between 24 hours and 7 days post coronary artery bypass graft and/or valvular surgery. Treatment with vernakalant effectively converted 47.0% of patients from AF to sinus rhythm vs. 14.0% placebo (p=0.0001).
In the AVRO, study vernakalant was significantly more effective than amiodarone IV in providing rapid conversion to sinus rhythm within the first 90 minutes of initiating therapy. In the AVRO study, vernakalant was demonstrated to be significantly faster than amiodarone IV in converting AF patients to sinus rhythm. In the trial, vernakalant was studied in 116 patients with AF (3 hours to 48 hours) vs. 116 patients on amiodarone. The amiodarone infusion was given over two hours (i.e., one hour loading dose of 5 mg/kg, followed by one hour maintenance infusion of 50 mg) with the objective to compare rapid conversion to sinus rhythm. The primary endpoint was the proportion of patients that achieved sinus rhythm for a minimum duration of one minute within 90 minutes of the first exposure of the study drug. In this study, treatment with vernakalant converted 51.7% of patients to sinus rhythm at 90 minutes vs. 5.2% with amiodarone.