Does J&J and BMS's Xarelto have a second chance for approval?

After a tough time in the early part of last week, on September 9, 2011, the FDA panel green-lighted Xarelto after FDA staff rejected it. FDA staff reviewers felt that Xarelto did not prove safety and efficacy for stroke prevention against Coumadin in the 14,000 Afib patients studied. But the FDA panel seems to see the data differently. The American Heart Association is also advocating Xarelto's approval.

Xarelto is already approved for prevention of clots in knee and hip replacements but in our data, cardiologists were skeptical in using Xarelto in their afib patients. And as treatment is likely for life, their concerns have a huge potential impact on their patients. There is no doubt that Coumadin/warfarin has problems but they are known problems and physicians seemed concerned about swapping known problems for unknown problems. And it seems that these specialists are expecting liver and/or bleeding problems with Xarelto

After reading a few transcripts of the FDA hearing, there do seem to be a few key issues that seem to need to be worked out even if approval is granted:

1. Some see that warfarin was not as skillfully used in the Xarelto pivotal trial, ROCKET, as opposed to other trials which makes it harder to evaluate Xarelto's comparative performance.
2. There seemed to have been a reasonably high number of discontinuations during the trial which made it hard to understand how to transition patients to another treatment from Xarelto.
3. Optimal dosage is not clear. Some panelists felt that twice-a-day dosage might be better than once-a-day.

Everyone did agree that the trial was well-designed and executed. But to me that makes the results more murky. One would think that a good trial would answer questions like this. And while the panel voted 9-2 for endorsing the drug, it was not resounding support. There are some that support efficacy parity with warfarin but not superiority. Is that enough? It could be if Xarelto's safety profile was stronger than warfarin.

One thing to remember is that anticoagulation is extremely complex and there may not be any completely solid answers to the outstanding issues. I do believe that if approved, many cardiologists will not be rushing to use the drug until more real world experiences can be reviewed.

A final FDA decision is due in November.

FDA says that J&J and Bayer's Xarelto has insufficient safety and efficacy data

Xarelto is the anticoagulant pill from J&J and Bayer. It was supposed to be a major blockbuster and compete with Pradaxa from Boehringer Ingelheim. Now analysts are saying that it might end up as a third line treatment behind warfarin and Pradaxa, if it even gets approval. The FDA is looking for more safety as well as more efficacy data in the prevention of stroke among Afib patients. Ouch. I think this is a big hurt for Bayer.

The market seemed surprised as the FDA seemed more upbeat about the product back in July.

Lovenox, which was the branded gold standard, is off patent this year so new products were highly anticipated. Coumadin/warfarin has been used for decades but it has bleeding, stop/start and food interference issues.

Having three drugs so close together in approval (Pradaxa, Xarelto and apixaban) was actually amazing since no new drugs have been approved since Lovenox.

Now, we did a review of anticoagulation back in October 2010. So looking back at the study, we did see evidence that cardiologists were critical of Xarelto's data and were worried about liver and non-major bleeding problems in their Afib patients. So I guess I am less surprised than others on this one.

At the time, we reported being less than enthusiastic with the data ourselves. I really am not a big fan of warfarin, mostly because physicians like to put patients on it for life and it restricts them so much in terms of having an active life. But is has been used for decades so anything replacing it really needs to be more safe and more effective, IMHO.