MSD (known in the and as Merck) (NYSE:MRK) and Cardiome Pharma Corp. (NASDAQ: CRME/ TSX: COM) announced that the intravenous (IV) formulation of ‘Brinavess’™ (vernakalant) has been granted marketing approval in the European Union (EU), and for the conversion of recent onset atrial fibrillation (AF) to sinus rhythm in adults.

The full indication is for the 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 new treatment has a unique mechanism of action from other AF medicines and is the first product in a new class of pharmacologic agents for cardioversion of AF to launch in the EU.

“‘Brinavess’ is the first and only agent that acts preferentially in the atria. This medicine offers physicians, patients and hospitals an important new therapy option to use for the rapid treatment of recent-onset AF, and we are pleased to add this to our strong portfolio of medicines for cardiovascular disease,” said Patrick Magri, senior vice president, general manager, Cardiovascular Franchise, Merck. “We welcome this important milestone in our collaboration with Cardiome and we are planning to make the product available in the EU by the end of the year.”

“‘Brinavess’ is the first pharmacologic innovation for recent onset of AF in over ten years, and European approval is an exciting juncture for Cardiome.” said Doug Janzen, president and chief executive officer of Cardiome. This success was made possible through the commitment and hard work of our employees and our partner Merck, the support of our shareholders, and the efforts of many dedicated medical professionals and patients who have taken part in the clinical program.”

Information on the clinical program for vernakalant

The approval of vernakalant is based on the results of three randomized, 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 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

Vernkalant is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Vernakalant also is contraindicated in patients with severe aortic stenosis, systolic blood pressure

Patients should be observed with assessment of vital signs and continuous cardiac rhythm monitoring during and after administration of vernakalant, until clinical and ECG parameters have stabilised.

Hypotension can occur in a small number of patients (vernakalant 7.6%, compared to 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 2 hours post dose (7.3% for vernakalant 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 vernakalant or placebo (3.2% for vernakalant versus 3.6% for placebo).

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

As a precautionary measure, it is preferable to avoid the use of vernakalant 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 (greater than 5%) seen in the first 24 hours after receiving BRINAVESS were dysgeusia (taste disturbance 20.1%), sneezing (14.6 percent), and paraesthesia (9.7%).

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

Before initiating therapy, the full prescribing information should be consulted.

Notes

About atrial fibrillation

Atrial fibrillation (AF) commonly leads to symptoms of fast heart rate, palpitations (being aware of the heart beat), shortness of breath and weakness and can increase the risk of developing a blood clot in the heart. If a blood clot in the atria leaves the heart and becomes lodged in an artery in the brain, a stroke may result. The risk of stroke in patients with AF has been shown to be 4-5 times that of the general population.1

Department of Health figures from 2007, suggest AF affects in excess of 600,000 people in the . This is now considered to be an under-estimate and that a more accurate figure may now be in excess of one million, with 200,000 patients being newly diagnosed each year.2 AF can affect adults of any age, but it is more common as people get older. In the over 65 year old age group, it affects about 10% of people.2

Merck-Cardiome Agreement

In April 2009, Cardiome and Merck announced a collaboration and license agreement for the development and commercialization of vernakalant. The agreement provides Merck, Sharp & Dohme Corp. (formerly known as Merck & Co., Inc.) with exclusive global rights to vernakalant oral formulation for the maintenance of normal heart rhythm in patients with AF, and provides another Merck affiliate, Merck Sharp & Dohme (Switzerland) GmbH, with exclusive rights outside of the United States, Canada and Mexico to vernakalant IV formulation for rapid conversion of recent onset AF to sinus rhythm in adults.

References

1. Kannal WB, Benjamin EJ. Status of the Epidemiology of Atrial Fibrillation.vMed Clin North Am 2008;92: 17-40

2. What is Atrial Fibrillation? Atrial Fibrillation Association; [Access on 02.09.10]

Source: Cardiome Pharma Corp.