Posted by Jeff Berk, BOLT International;
In March Eliquis got the nod from EMEA for use in preventing venous thromboembolic events in adult patients who have undergone elective hip or knee replacement surgery. Ho-hum. The real action is in stroke prevention in atrial fibrillation. To the point, we expect ARISTOTLE to publish “any day” now. Soon, anyway. Rather than waiting until it happens, and making all sorts of “insightful” comments about what the results for SPAF mean, how’s about we publish TODAY what BOLT’s Cardiology Thought Leader panel thinks of the drug – and then we can all see how well they prognosticated. BTW, we’re starting our next cycle talking with our experts about antithrombotics and antiplatelets. If you have anything that you want to ask them, email me!
Eliquis (apixaban; Bristol-Myers Squibb / Pfizer)
- Once ARISTOTLE is published we believe that the marketing message for Eliquis will be “One drug for everybody with a-fib, regardless of whether they are candidates for warfarin or not”. The tag line for Eliquis for SPAF will be: “Safe, low bleeding rates and no off-target effects”.
“One thing they could do is actually show that granted we have talked about how aspirin is straw man, but the reality is that they have actually shown that they are better and the trial was stopped early. They could actually come at it from an angle and say we are better than both antiplatelet therapy. So for those patients in your clinic who have atrial fibrillation that you are not putting on warfarin and you are just putting on aspirin, ours is a better drug and we are better than the patients that you have on warfarin. So we are sort of a one stop solution for everybody with a-fib, whether they are candidates for warfarin or not. And that is a fairly powerful message I think. As you know, physicians use all kinds of excuses not to put patients on warfarin.
- ARISTOTLE will bring Eliquis onto a level SPAF playing field with Pradaxa. The study will publish in April 2011. ARISTOTLE is a comparison of apixaban 5.0 mg twice daily vs warfarin. AVERROES showed that the apixaban bleeding rate is extremely favorable compared to warfarin. It is certainly to be as good as that of dabigatran 110. Based on publicly discussed interim results from ARISTOTLE, it is possible that apixaban is going to have an even nicer looking safety profile than dabigatran, with an even bigger reduction in major bleeding, a very low rate of intracranial bleeding, and probably no increase in GI bleeding or MI signal. Given however that APPRAISE2 (adding apixaban onto dual antiplatelet therapy for ACS) was stopped early, there is clearly some increased bleeding effect with apixaban too. Thus, we predict that Eliquis will be “better” than Pradaxa 110, but not as efficacious as Pradaxa 150. And we predict that Eliquis will be safer than Xarelto, but in ARISTOTLE, not squeaky clean on bleeding.
“It looked great, but will it look the same in ARISTOTLE and how will it match up to ROCKET? The comparison will likely be to ROCKET because that is the most recent study before ARISTOTLE. I am not sure. I think apixaban has a knock against it in that we know that the APPRAISE 2 trial was stopped early for ACS. We don’t know the details behind that, but I think that is probably in the back of everyone’s mind. I think those details will be forthcoming some time this year. I think the bleeding aspect when compared to warfarin is clearly going to be likely the distinguisher between rivaroxaban and apixaban”.
“There will be ARISTOTLE. If we were just left with AVERROES I think that it would be challenging, but of course we are not. So that is good. Given what you know today and what you can speak to, help me do the comparison of dabigatran to apixaban? We don’t know really. But the signal that we are getting from AVERROES is that the bleeding rate on apixaban is going to be extremely favorable compared to warfarin. It is certainly to be as good as that of dabigatran 110, and possibly better. It is not inconceivable at all that it is going to have an even nicer looking safety profile with an even bigger reduction in major bleeding, very low rate of intracranial bleeding, probably no increase in GI bleeding. I am saying of this based on the AVERROES results that you have seen. That is all good news. So really the big question is do they actually grab the brass ring? If they are safer than warfarin but have greater efficacy then they are the winner, right? No MI signal, no GI intolerance, better tolerated than aspirin, great bleeding and superiority to warfarin well then they are going to basically be the number one. That is the big question that we are waiting to hear and we won’t know until September. If you want my opinion I think that it is not for sure that they are going to achieve that. They may just get noninferiority. In which case they are still going to be looking good. They are going to have, as you put it, what looks like an extremely safe drug. Is it going to look absolutely clearly better than dabigatran 110? Maybe, maybe not. My guess is that it is going to look like dabigatran 110 actually, but without the GI issue and without any concern of MI. So is going to be sitting pretty? A lot prettier than rivaroxaban”.
“I think the thing that was impressive, at least if you look at the AVERROES results was there was no difference in bleeding. Now are we going to see the same thing in ARISTOTLE? Perhaps, but that is not certain. And I am not clear on exactly what the risk features of the ARISTOTLE population would be compared to what was seen in ROCKET. I think the bleeding issue could be a way that really distinguishes the two drugs, for example. But I think that apixaban is going to have a high hurdle to clear with the results from ROCKET and rivaroxaban”.
“All we know is that the trial wasn’t stopped, while APPRAISE was stopped, which is encouraging I guess in terms of safety. I don’t know that you can say much beyond that. I find it hard to believe that it won’t also be approved. I just think these drugs seem quite similar overall. I would be surprised if they hit a homerun in ARISTOTLE versus warfarin. We know that it looks favorable compared to aspirin, but that is no big surprise. We know how this story is going to unfold. It has been incredible consistent antithrombins better than antiplatelets and combinations with antiplatelets cause a lot of bleeding. And overall these agents don’t blow warfarin away but they appear to be a little safer, particularly with regard to intracranial hemorrhage. I would expect the same thing frankly. Based on the pharmacokinetics of apixaban I would be surprised if there is any meaningful difference. I think the differences probably that you see with certain indications and certain trials are just the vagaries of how the trials were set up and chance”.