12:00 AM
 | 
Dec 17, 2007
 |  BioCentury  |  Regulation

Kynapid: A matter of benefit

Regulation

Kynapid: A matter of benefit

Once it resolved existential questions about the role of drugs in treating atrial fibrillation, the Cardiovascular and Renal Drugs Advisory Committee's deliberations on Kynapid vernakalant from Cardiome Pharma Corp. and Astellas Pharma Inc. came down to a straightforward risk-benefit calculation in favor of approval.

Last week's meeting was dominated by debates about the benefits of using any drug to rapidly convert AF to sinus rhythm, and the acceptability of short-term endpoints to demonstrate efficacy(see Cover Story).But while changing views within FDA about these basic issues have made a moving target of Kynapid's approval requirements, the committee's 6-2 vote to recommend approval may stabilize the regulatory foundation under the product.

If FDA adheres to the recommendation, Kynapid is likely to be widely used to treat the condition, according to advisory committee members.

Getting to data

Kynapid, a mixed ion channel antagonist, was developed by Cardiome (TSX:COM; CRME, Vancouver, B.C.) and Astellas (Tokyo:4503, Tokyo, Japan).

Astellas has North American rights, conducted one of the Phase III trials that provide efficacy data for the NDA, and is responsible for U.S. regulatory activities.

COM and Astellas have completed two Phase II trials and the ACT I and III Phase III trials of Kynapid. In addition, they have a pair of ongoing Phase III trials: ACT II, which is studying Kynapid in post-valvular or coronary artery bypass graft surgery patients, and ACT IV, an open-label study.

Kynapid's efficacy was clear based on the 56-patient dose-ranging Phase II study, which achieved a statistically significant (p=0.0015) increase in the number of subjects in sinus rhythm at 60 minutes vs. placebo despite the small size of the trial (36 patients in the Kynapid arm). The median time to conversion to sinus rhythm (cardioversion) was 14 minutes.

The Phase III program was intended to confirm the Phase II efficacy and characterize safety.

When COM met with FDA at the end of Phase II meeting in April 2003, the agency agreed Kynapid could be approved based on the demonstration of cardioversion for any length of time in about 600 patients.

Two and a half years later, FDA told Astellas that it had second thoughts about the size of the safety database. At a pre-NDA meeting in November 2005, the Cardiovascular and Renal Products Division "expressed its concern regarding the small number of subjects in the program, acknowledging their previous agreement on the proposed number of exposed subjects, but warned...

Read the full 2048 word article

User Sign in

Trial Subscription

Get a 4-week free trial subscription to BioCentury

Article Purchase

$150 USD
More Info >