麻豆传媒

More than a decade since its first shot at FDA approval, vernakalant injection will once again face an advisory panel for an indication in rapid conversion of recent-onset atrial fibrillation (Afib).

The agency's Cardiovascular and Renal Drugs Advisory Committee will convene Tuesday to discuss whether to approve the multiple ion channel blocker and any potential restrictions that should be placed on its use. Specifically, they will consider two indications for the IV antiarrhythmic:

• Non-cardiac surgery patients in Afib for 7 days or less
• Post-cardiac surgery patients in Afib for 3 days or less

A 2007 vote by FDA panelists had for the drug (its marketing application then sponsored by Astellas and Cardiome, now Correvio).

The agency, however, ultimately decided in 2008 that although vernakalant was effective in cardioversion according to the ACT I and ACT III trials, its before hitting the market.

The decision stemmed from eight serious adverse events -- namely events related to hypotension, arrhythmias, and conduction disturbance -- occurring within 2 hours of vernakalant infusion in a study population where such poor outcomes were not expected.

Making matters worse, a case of cardiogenic shock occurred in one patient in the subsequent ACT V study, prompting the FDA to place vernakalant on clinical hold in 2010.

This meant a ban on all administration of the drug in clinical studies in the U.S., a ban that stands to this day.

In 2011, Merck the development of the drug and tried unsuccessfully to persuade the agency to remove the ban. It returned all rights to the drug to Cardiome , which is now known as Correvio. The company resubmitted vernakalant to the FDA .

The new application includes data from four phase III studies (ACT IV, ACT V, , and the Asia-Pacific Study) and five pharmacokinetic studies conducted since the original New Drug Application was submitted in 2006. There are now a total of eight phase III studies for the FDA advisory committee's discussion.

In addition, the sponsor now has post-marketing safety data from Europe, where the drug was approved in 2010 under the brand name Brinavess, and elsewhere around the world.

"Indirect comparisons with other drugs and electrical cardioversion (ECV) suggest that vernakalant is less safe than existing treatment modalities. Hence, this meeting will focus on the safety issues identified in the vernakalant development program and whether available data support a favorable benefit-risk profile of vernakalant," according to FDA for tomorrow's panel discussion.

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