Rivaroxaban - the Next Warfarin?

[tobagotwo]

Excerpts from recent clinical trial information:

FDC Reports: Health News Daily - October 24, 2006
Barcelona - The oral direct factor Xa inhibitor rivaroxaban performed favorably in a pair of large phase II randomized clinical trials presented at a joint meeting of the European Society of Cardiology and the World Heart Federation.
The two multinational trials totalled 1,155 patients with acute deep vein thrombosis (DVT). Each 3-month study showed oral rivaroxaban to be as effective at reducing thrombus burden and preventing pulmonary embolism or recurrent DVT as was standard therapy with unfractionated or low-molecular-weight heparin transitioning to warfarin.
Major bleeding rates were similarly low in patients on the various rivaroxaban doses studied and with standard therapy. And there was no hint of a liver toxicity problem with rivaroxaban in either study. That's encouraging because liver toxicity proved the undoing of ximelagatran (Exanta), a once-promising potential alternative to warfarin which AstraZeneca was forced abandon...
...Rivaroxaban is a pharmacokinetically predictable drug. It is administered in a fixed oral dose without need for the frequent coagulation monitoring and dose adjustments that make warfarin therapy such a hassle, he explained...
...The incidence of abnormally elevated liver function tests during the first 21 days was 10-fold greater in the warfarin arm than in patients assigned to rivaroxaban. Thereafter, rates of liver function abnormalities were similarly low in warfarin- and rivaroxaban-treated patients.
Rivaroxaban is the subject of an ongoing phase III trial for primary prevention of venous thrombolic events after major elective orthopedic surgery. Other large phase III trials are planned for stroke prevention in patients with atrial fibrillation, as well as for treatment and secondary prevention of DVT.
The phase II studies were sponsored by Bayer HealthCare and Scios Inc.
By Bruce Jancin
Elsevier Global Medical News
Copyright FDC Reports Inc. 2006
<http://www.fdcreports.com>

If this drug should pan out, it may offer more simplicity than Coumadin (warfarin). However, even if successful, it will take years to clear the FDA for valve use, and the true safety profile won't be known for years after that, due to the surprises that happen when 1,000,000 people are taking it for 30 years, vs. 400 taking it for a few months. No clinical trial can mimic that enormous and stark reality.

Best wishes,

 

[Guest]

Thanks. This is a good assessment of the drug. The main point is that nobody should base a valve choice decision on what may happen years in the future. It is also another reason why I don't think that it smart business to be developoing genetic tests for warfarin - the life is going to be too short.

 

[LUVMyBirman]

Personally banking on future increased technology. Something that has a 30+year longevity without the need for anticoagualtion! According to the "estimated" time frame my card has given for a redo....they have 20 years to figure it out

 

[Guest]

My guess is that there will not be a replacement for warfarin. There will be many replacements for warfarin. When the big profit niches (Atrial fibrillation and blood clots in the legs) are full of competitors then companies will turn to niches such as mechanical valves and lupus, etc.

This is a oversimplified because valve research is trying for technology that does not require anticoagulation.

 

[Guest]

I just thought some more about rivaroxaban and liver toxicity.

They had 1,000 + people tested for three months.

The Exanta study had 3,000 people for about 6 months. 1 of these people died of liver toxicity. So this rivaroxaban study was not big enough or long enough to uncover fatal liver toxicity at the same level as Exanta caused. In fact, it would have been quite unusual if they had found fatal liver toxicity at this level.

 

[tobagotwo]

Exactly - time and volume are the keys. Both must be there to learn the safety factors. It's highly critical in this type of usage, as it's daily and required.

Phase three trials mean it's well on the way to its first FDA test for that indication (DVT).

It would be nice if it turns out to be at least as efficacious and safe as warfarin, without dosing issues and with greatly reduced testing.

Time and patients will tell.

Best wishes,

 

[barbwil]

riv a rox a ban Hopefully they'll come up with a shorter name before I

have to ask for a refill!

I know what you're thinking---you're 76 yrs old so don't worry about it!!!

 

[Guest]

So far Bayer has not given it a brand name. It will get catchier and easier.

Warfarin is working Barb, that is the real reason to not worry about it. It will be 17 years after it was patented before you have to order by generic name.

 

[gijanet]

Oh, how I wish!!!!

Oh, how I wish!!!!

Thanks, Bob, for posting this and keeping us informed. I realize this isn't happening tomorrow, but I pray that Katie has alternatives in her lifetime, if not mine!

Earlier tonight, when Katie got out of the bathtub, I looked at her little bruised body (noggin still bruised from two weeks ago or is it three now, a four inch bruise on her right hip, right elbow bruised, left knee and shin bruised) and wonder if we did the right thing going mechanical.........

With her medical history (based on our last surgical adventure, I really don't know if she can make it through a sixth surgery, but I can't go there - she'll just have to when that day comes, which I pray is many, many years from now), I know we had no real choice, but I so wish there were alternatives to coumadin besides the obvious....................sigh!

Thanks again. HUgs. J.

 

[Guest]

Janet,

There is no doubt that there will be a replacement for warfarin for valvers within the next 10 years.

If I were to place a bet, I would bet that she is gaining strength every day. A 6th surgery might have been impossible at one time but several years in the future is another story.

 

[gijanet]

Al, Do you really think so?

Al, Do you really think so?

There is no doubt that there will be a replacement for warfarin for valvers within the next 10 years.

Even with FDA approvals and all? Even for mitral valves (Katie's isn't really a mitral, but I guess that's the closest!)? Does that mean that there are some trials going on now that you are privy to, but can't talk about. 'Course as much as I would like to see Katie off of coumadin, I would not be willing for her to be a guinea pig this time. We have participated in our fair share of studies, but not in this case.............

If I were to place a bet, I would bet that she is gaining strength every day. A 6th surgery might have been impossible at one time but several years in the future is another story.

Thank you, Al, so much for saying that. I needed to "hear" that. I try not to dwell on these things, but sometimes it just "gets to me" and comes rushing out. Many hugs. J.

 

[Guest]

I don't know of any trials underway. I am basing my guess on how many drugs there are under way to replace warfarin. The market is going to get very crowded and somebody is going to have to concentrate on heart valves in order to make any money.