Here are answers to some of your q's tuck. The last one is int for me since this ACT1 pt is a protocol violation and FDA will be questioning Cardiome abt the pt. I don't see it as an approvability issue but hopefully Cardiome won't repeat the same mistakes with the oral version.
Cheers...Praveen
David Martin
Okay. What about the question of rate control versus rhythm control? What drives that treatment decision now and could vernakalant change the paradigm?
Dr. Jeremy Ruskin
Well I don’t think vernakalant will change the paradigm there. I think that’s a function of education. There has been I think a movement towards more rate control than rhythm control as a result of the AFFIRM study but I think that’s largely a misinterpretation of the results and for us the bottom line is that people whose AF is causing symptoms—and that’s a very substantial percentage of people with a-fib—deserve a trial, one or more trials of rhythm controls to see if they feel better. And if they feel better, many of them will accept a modest risk associated with a pharmacologic agent to be in sinus rhythm and to feel better.
What AFFIRM taught us is that we don’t have a good rhythm control strategy that’s safe and effective, but if we had one my bet is that the vast majority of people in AF would do better and feel better in sinus rhythm. So for us it’s driven largely by symptoms and age. You know, the younger the age the more aggressive we are about trying to restore sinus rhythm. And I think that paradigm has got to change as a function of education and the availability of better, safer drugs. Hopefully vernakalant will be one of those, but I think there are a number of things in the pipeline and my bet is that if you could do AFFIRM over again with a really safe pharmacologic option for rhythm control that there wouldn’t be any doubt about the outcome.
Even AFFIRM documents the fact that sinus rhythm, you know, there were only two predictors of survival of AFFIRM, one is being on coumadin and the other one is being in sinus rhythm. So if you look at it by treatment assignment, the rhythm control arm clearly does no better than the rate control arm, but that’s because of the complications of the drugs not because sinus rhythm is not better for you.
David Martin
In ACT 1 we saw one potentially drug-related death. I believe it was in a patient who was in active MI prior to receiving the drug and, you know, therefore it appears there were other causes contributory to the death and, in fact, I think based on the inclusion/exclusion criteria of the trial it was a protocol violation. Despite those explanations, does the FDA get hung up on things like this to the point where they might not approve the drug?
Dr. Jeremy Ruskin
Well I think you’re right about that case in the sense that the case involved a series of protocol violations, and that’s clear cut. Nevertheless, when a complication occurs in a protocol, you know, whether it’s a drug or device, the drug or the device owns that complication. So do I think they will pay attention to it and that they will drill down on it? Yes. Do I think it reaches the level of an approvability question? No. But again, I’m giving you personal opinion based on what I know about the case. So these kinds of things are always disconcerting when they happen because what I think this reflects is the potential for problems when a drug is misused. And that was the case here. The FDA is going to pay attention to that. But do I see it as an approvability issue? I personally don’t. |
