Hello, I'm Dr. Deepak Bhatt, director of the Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster professor of Cardiovascular Medicine in New York.
In the REVERSE-IT trial, we studied bentracimab, which is an intravenous monoclonal antibody that binds to the antiplatelet agent ticagrelor, and then that complex is removed from the circulation. So it's a way in patients who are receiving ticagrelor, who need emergency surgery or who are having bleeding complications to reverse the effect of ticagrelor.

Now, it's an investigational agent, but what I presented at the American College of Cardiology were the final results of this phase three trial known as REVERSE-IT.
Ticagrelor is, of course, a very popular antiplatelet agent. Multiple trials support its use across a variety of therapeutic areas, and pretty soon it'll be going generic worldwide, so its use will only increase. But as is the case with every antithrombotic and every antiplatelet agent, there is a risk of bleeding.

Ticagrelor is a reversible antiplatelet, meaning that it binds to the ADP P2Y12 receptor reversibly, and as a consequence of that, platelet transfusions don't reverse its action. But as a consequence of that, we have been able to detect, develop this monoclonal antibody that does reverse its effects.

And what we found in the REVERSE-IT trial, which again is a phase three trial, was that it restored normal platelet function, essentially in all the patients, in the surgical patients, in the patients having major bleeding complications who had been on ticagrelor.
So if the FDA and other regulatory agencies, hopefully in the future, EMA and so forth, opined favorably, then it would hopefully be able to be used in patients. But for right now, it's an investigational agent.

In addition to examining platelet function test, we also did examine bleeding as assessed by independent adjudicators. And in the overall trial, the rates of effective hemostasis were quite high. Specifically, in the surgical patients, it was 100% that they adjudicated as having attained effective hemostasis. In the bleeding patients, it was 83%.

Well, we're still analyzing data from the phase three trials. We have to finish our analyses and of course, you know, get the work published. The FDA will have to review the data, and we'll have to see if they want, you know, other things beyond just the data from the REVERSE-IT trial.

There had been a previous phase one trial. I'd actually presented that as a late breaker at ACC a few years back. That work was published in the English Journal of Medicine, and that was a randomized trial of healthy volunteers. As phase one trials are randomized to bentracimab or to placebo, and that showed a significant and rapid restoration of normal platelet function. But that's healthy human volunteers.
So here, this is the phase three trial that I just presented. Reverse it to see if what we saw in that randomized trial of healthy human volunteers actually played out in real patients, either needing emergency surgery or with life threatening bleeding. And indeed, it did play out the same as in the healthy human volunteer. So now we know that it does what it's supposed to, restore normal platelet function. Patients on ticagrelor.
In terms of other data that'd be useful, there's even phase two data that we still have to fully analyze and get published and so forth. So hopefully there'll be a lot more data to come.

Beyond that, I think real world analyses would be useful just to see exactly what sort of bleeding rates there are in patients on ticagrelor that are having emergency surgery. Patients on ticagrelor, what the rates in real life are of spontaneous major bleeding, what the rates of intracranial hemorrhage are.

In the REVERSE-IT trial, for example, we had 20 patients that had intracranial hemorrhages and 80% of them attained successful hemostasis, which is a pretty good number compared to historical controls.