I told you how we think we figured out how to get efficacy greater than what has been seen before and really identify the patients who truly need the medication or extended duration prophylaxis. There is the important side of it. It is not only patient selection, it is always dose.
This is the model data. When we did our Phase 2 clinical trial, what we did is we tried to analyze a really important PD market to pick our dose. You know we did is we modeled or we assessed thrombin generation inhibition, so all these drugs inhibit. They all inhibit the generation of thrombin. We took what is currently a very well-established standard by warfarin. Warfarin was used in our Phase 2 clinical trial. Simply what you want to do is you want to get a level of inhibition of thrombin generation, above that which can be measured by an INR which is well-established with warfarin. You want to get more than two from an INR reading because that is what allows you to prevent clot, but you do not want to exceed three because that is when you get bleeding.
When we had our 80 mg dose in our Phase 2 trial – this is the PDcurve right here –we wanted to kind of stay within that range. We wanted to get a lot of it early on, a nice bolus of it because we are in the acute setting and then we wanted to sustain that with once-daily dosing. How is that different than an apixaban dose or a Xarelto dose in this indication? Here is the Xarelto dose. It has a wide variation in fluctuation, has a very high concentration very early on because that is a short half-life. You got to give a lot of it. You got to give a lot of it for it to be around for 24 hours. Then you see the apixaban dose. It has got a BID profile. If you start to administer it without a good bolus in the beginning, you start to see you have a little bit less, maybe, of where you want to be.We think, in this indication previously, it is our hypothesis. It is our hypothesis that Xarelto is a little bit overdosed and apixaban was a little longer dosed. What we said is we picked a better patient population for having higher events and we think we got the dose a little bit better.
If we are successful, this is the… boy, there is just not too many value proposition throughout there in the pharmaceutical business or biotech business right now. We can build a billion dollar franchise with a clear value proposition that says we prevent clots and deaths associated with these blood clots. We can reduce hospitalization, readmission costs, and we can do it at an acquisition cost that is lower in the United States than the generic price of the standard of care. There are not too many drugs that can say that. That is why we think it is such a compelling value driver for this company over the longterm.
Andexanet alfa, this is the antidote. It is real clear now that what we had projected many years ago is starting to happen and Jason, you asked about it. The hospital admissions due to bleeding, they are going to up. If you look at the 12 months, September-to-September of 2013, March-to-March of ‘12 to ‘13, the hospital admissions in factor Xa inhibitor-treated patients went from about 17,000 to 30,000 and that is just Xarelto and Eliquis, just those two. Lovenox is staying about the same because itsuse is kind of flattening out. As the use grows, so does this piece of the pie.
