Transcript – Discussion of the Clinical Evaluation of the COBRA PzF NanoCoated Stent – Dr. Philip Urban

Dr. Donald Cutlip:

Hi, I’m Don Cutlip from Boston, Massachusetts. I’m here with Dr. Philip Urban from Geneva, Switzerland, and the Principal Investigator of the LEADERS FREE trial. Welcome, Philip. And we’re going to talk today about the eCOBRA results, and a bit about the clinical development from the COBRA PzF NanoCoated Stent.

Dr. Philip Urban:

Yes, absolutely. Hi, Don. Nice to see you here in Paris. Yeah, the eCOBRA was presented just two days ago by Luke Maillard, who is the PI from France, in the South of France. And, there are several really interesting, and quite impressive, aspects to that large registry. It’s French. It’s prospective, multicenter. They got very close to 1,000 patients. So, that’s quite something. And the methodology I think has been quite strict. They’ve had a sort of independent CEC, and independent angiographic reviews. It’s quite solid, in that respect. And yes, I think many of the results are extremely interesting.

But perhaps before that, Luke tells us that they feel they’ve selected patients that are close to the LEADERS FREE population. And certainly looking at the mean age, I think it’s in the range of 75, that does fit that bill. We don’t have quite enough information to make quite sure how comparable the populations are. But, they are defined in a very simple, operational way as non-DES candidates. Of course, I guess that could vary from center to center, but yes. They’ve got good, solid follow-up, with excellent numbers. Hardly anyone lost a follow up, out to one year.

Dr. Donald Cutlip:

And they had a high rate of acute coronary syndrome patients, as well.

Dr. Philip Urban:

Very important. Absolutely. I think it was in the range of 40 or 50% of patients presenting with either non-STEMI or STEMI. Yeah, you’re right. Very important to make that point.

And one of the numbers that I was impressed of, very favorably, was the need for repeat revascularization. I mean, that was in the… just above 4% one year. And when you think that what we know of the late loss with this device, it’s not a drug-eluting stent. Its major feature is its thromboresistance. I think that that TLR is really, quite spectacularly good. So this is real life, in France. There’s no problem to re-cath people, if they need it. So they would’ve had it, if they had needed it. So that’s the number that to me is most encouraging.

There are a number of other numbers that are interesting. The stent thrombosis was 1.2 definite and probable at one year. It is an important point because, you can either be an optimist and say, “In LEADERS FREE it was more than 2%. So if these are roughly the same patients, this is telling us something.” If on the other hand you say, “Yes, but this stent is supposed to be supremely thromboresistant. Then is that number still as good as you could have hoped for?” I think the investigators are going to have to look into that data in great detail. Find the relationship between DAPT duration, and the thrombotic events. Whether MI, stent thrombosis, and so on. And tease out more information. It’s probably there for us to find, but we haven’t yet seen it. This is a preliminary analysis.

Dr. Donald Cutlip:

I mean, I think that’s a great point because since there was a registry, that there was not so much protocol driven, DAPT duration. So I think investigators were doing different things. Some got single antiplatelet therapy. Sometimes it was only two or three weeks. And whether that has any impact on stent thrombosis. I think that would be important to sort out.

Dr. Philip Urban:

Absolutely. And I think we shall. I think Luke was quite positive that he could eventually get that information. They’ve only just finished looking at… having a first look at this dataset. And so we will eventually have that information.

Dr. Donald Cutlip:

I think, it was important for them, obviously, to present the results here, and he just has seen the data. So I think we’re both confident that he’ll go back and the investigators will go back, and look at these other questions.

Dr. Philip Urban:

Absolutely. I guess, if we’re looking at some of the limitations of the registry, another element that I believe may not be fully available, is the amount of bleeding there will have been. And you could argue that, so what, they’ve probably done that as short as DAPT as they possibly could. And that was because of their concern about bleeding, but it would have been nice to have some numbers on the bleeding. And again, I believe that both the investigators, and the sponsors, are hopefully going to look into what information they can find regarding that. I think it would be a nice balance to have the thrombotic complications and the balance, and at least some of the major bleeding complications.

Dr. Donald Cutlip:

I agree. So CeloNova is running another important study, COBRA-REDUCE, an international randomized trial. Can you tell us a little bit more about that study? Especially your impression of the design, and what we may hope to learn from those results?

Dr. Philip Urban:

It’s a very impressive, very ambitious design and it’s potentially game-changing because they’re going for 1,000 patients on oral anticoagulants. And the idea is to… The patients will be randomized to either a drug-eluting stent, and the standard guideline driven three to six months, from what I understand currently, DAPT. Or, the COBRA Polyzene stent, with only two weeks of dual antiplatelet therapy. Which is extremely, aggressively low. And so, it will be… there will be two end points. The main primary end point is to see whether the bleeding can be decreased in terms of superiority. Which I would think can be pretty, obviously, reached. And then they obviously have to balance that with a non-inferiority in terms of thrombotic complications. And this is ongoing, and I understand that it’s in excess of 400 patients and recruitment was slow to begin with, and it’s picking up. So certainly we hope that this trial will shed some more light. It could be a very important addition to our options in these patients.

Dr. Donald Cutlip:

So maybe I’ll just comment on the role of a COBRA PzF in practice. Do we have enough clinical data at this point where we can advise clinicians, put this on the shelf and use it during X, Y, and Z? Or do you think we just need more information?

Dr. Philip Urban:

I would say, for today, from what I understand, and correct me if I misunderstood something, but I believe the device is available in the US with a one month label. So if I was a US physician, I think this would be a very good choice for the patient who needs urgent, major surgery, who really had a recent nasty bleed. The sort of LEADERS FREE patient now in the US, I would be quite happy to go with this stent and one month. In Europe, if I can have the BioFreedom for the moment, I prefer the BioFreedom, because I have more data. But this may very well be a perfectly viable alternative. Or perhaps even better because two weeks is shorter than one month. And that’s something to think about it.

Dr. Donald Cutlip:

Yeah. I mean, I think there’s two interesting points or parts of this. And one is the antithrombotic opportunity with shorter DAPT. And I think we need more information on that. Aloke Finn was here before you and talking about some of the preclinical healing data, in terms of endothelial function, and maybe as a prevention for new atherosclerosis. Obviously, we need a lot more evidence for that, but it might be another place the stent would come into play. In those patients who are not at high risk for restenosis, perhaps.

Dr. Philip Urban:

I was actually impressed by Aloke’s data and he’s probably discussed it much more seriously than I can possibly do. But, in his ex-vivo shunt model, where he puts in a sequential order of different stents, you see platelets that adhere in large numbers. Both to polymer-coated drug-eluting stents, and to bare metal stents, but not to the COBRA. And so, to me despite the relatively high late loss, this device does seem to have antithrombotic properties, which are unique. At least in Aloke’s model, it’s very clear. And that’s why I think this device may have a big future, but it’s a little early to say.

Dr. Donald Cutlip:

Very good. Okay well, it was very nice talking to you about the device, and thanks for stopping by.

Dr. Philip Urban:

My pleasure, thank you Don.

Dr. Donald Cutlip:

Good to see you, take care.