Merck to Acquire Rights to Vernakalant i.v. in Canada, Mexico and the United States from Astellas

Merck (NYSE:MRK), known as MSD outside the United States and Canada, and Astellas US LLC (“Astellas”), the U.S. subsidiary of Astellas Pharma Inc. (Tokyo:4503) today announced that they have entered into an agreement under which Merck, through a subsidiary, will acquire the exclusive rights to develop and commercialize the investigational intravenous formulation of vernakalant (vernakalant i.v.) in Canada, Mexico and the United States from Astellas. Vernakalant i.v. is currently approved in more than 10 European countries for rapid conversion of recent onset atrial fibrillation (AF) to sinus rhythm.

“Atrial fibrillation represents a large and growing unmet medical need,” said Dr. Michael Mendelsohn, senior vice president, franchise head, cardiovascular and atherosclerosis research at Merck. “With this agreement, Merck has secured worldwide rights to vernakalant i.v. This is an important step as we seek to expand access for patients in need.”

Under the terms of the agreement, Merck will pay Astellas an undisclosed upfront fee. In addition, Astellas will be eligible for milestone payments associated with development and regulatory approval as well as sales thresholds achieved in Canada, Mexico and the United States.

“We continue to strengthen our capabilities in core therapeutic areas and steadily make progress on our vision of becoming a Global Category Leader,” said Masao Yoshida, President and CEO, Astellas US LLC. “In reviewing the priorities of our North American development programs, Astellas has decided to divest its rights for vernakalant to Merck.”

In October 2003, Astellas US LLC was granted an exclusive license to develop and commercialize vernakalant i.v. in Canada, Mexico and the United States by Cardiome Pharma Corp. In April 2009, Merck, through a subsidiary, was granted exclusive rights to vernakalant i.v. outside of Canada, Mexico and the United States for rapid conversion of acute atrial fibrillation to normal heart rhythm.

About vernakalant in the EU

In September 2010, Merck was granted marketing approval in the European Union (EU), Iceland and Norway for the intravenous formulation of BRINAVESS™ (vernakalant) for rapid conversion of recent onset 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.

The EU approval of BRINAVESS was based on the results of many clinical studies. In the ACT I and III studies, the efficacy of BRINAVESS at converting patients from AF to sinus rhythm for a minimum duration of one minute within 90 minutes of initiating therapy was evaluated in 390 haemodynamically stable adult patients with short duration AF (3 hours to 7 days) versus placebo. In ACT I, vernakalant cardioverted 51.0 percent of patients versus 4.0 percent of patients taking placebo (n=74 and 3, respectively; p<0.0001). In ACT III, vernakalant cardioverted 51.2 percent of patients versus 3.6 percent 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. In the AVRO study, BRINAVESS was significantly more effective than amiodarone IV in providing rapid conversion to sinus rhythm within the first 90 minutes of initiating therapy. In this study, treatment with BRINAVESS converted 51.7 percent of patients to sinus rhythm at 90 minutes versus 5.2 percent with amiodarone.

BRINAVESS is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. BRINAVESS also is contraindicated in patients with severe aortic stenosis, systolic blood pressure <100 mm Hg, and heart failure class NYHA III and NYHA IV. Furthermore, BRINAVESS is contraindicated in patients with prolonged QT at baseline (uncorrected >440 msec), severe bradycardia, sinus node dysfunction, or second-degree or third-degree heart block in the absence of a pacemaker. BRINAVESS is contraindicated in patients who use intravenous rhythm control antiarrhythmics (class I and class III) within four hours prior to administration of BRINAVESS. In addition, the use of intravenous rhythm control antiarrhythmics (class I and class III) is contraindicated within four hours after administration of BRINAVESS. BRINAVESS is also contraindicated in patients with acute coronary syndrome (including myocardial infarction) within the last 30 days.

Patients should be observed with assessment of vital signs and continuous cardiac rhythm monitoring during administration of BRINAVESS for two hours after the start of infusion and until clinical and ECG parameters have stabilized. Frequent monitoring of blood pressure is also required during and at least 15 minutes after the completion of the infusion.

Hypotension can occur in a small number of patients (vernakalant 7.6%, placebo 5.1%). Hypotension typically occurs early, either during the infusion or early after the end of the infusion, and can usually be corrected by standard supportive measures. Patients with congestive heart failure (CHF) have been identified as a population at higher risk for hypotension.

Patients with a history of CHF showed a higher incidence of ventricular arrhythmia in the first two hours post dose (7.3% for BRINAVESS compared to 1.6% for placebo). These arrhythmias typically presented as asymptomatic, monomorphic, non-sustained (average 3 to 4 beats) ventricular tachycardias. By contrast, ventricular arrhythmias were reported with similar frequencies in patients without a history of CHF who were treated with either BRINAVESS or placebo (3.2% for BRINAVESS vs. 3.6% for placebo).

In patients with valvular heart disease, there was a higher incidence of ventricular arrhythmia events in patients on BRINAVESS. These patients should be monitored closely.

As a precautionary measure, it is preferable to avoid the use of BRINAVESS during pregnancy. It is unknown whether vernakalant/metabolites are excreted in human milk. Caution should be exercised when used in breast-feeding women.

In clinical studies, the most commonly reported adverse reactions (>5%) seen in the first 24 hours after receiving BRINAVESS were dysgeusia (taste disturbance) (20.1%), sneezing (14.6%), and paraesthesia (9.7%).

Clinically significant adverse reactions observed in clinical trials included hypotension and ventricular arrhythmia.