Antidote for Rivaroxaban ! and mention of Apixaban

[iris1205]

Antidote Reverses Anticoagulation Activity of Rivaroxaban: ANNEXA-R

Michael O'Riordan

January 09, 2015

SAN FRANCISCO, CA — Portola Pharmaceuticals, the makers of an antidote for rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals), a factor Xa inhibitor that is part of the newest generation of oral anticoagulants, announced today that a phase 3 study testing the safety and efficacy of the antidote met its primary end point[1].

In the trial, an 800-mg intravenous bolus of andexanet alfa, which was tested in 41 healthy volunteers treated with rivaroxaban 20 mg for 4 days and then subsequently randomized to the study drug or placebo, "immediately and significantly" reversed the steady-state anticoagulation activity of rivaroxaban.

The full results of the study, known as ANNEXA-R, are scheduled for presentation on Monday, March 16, 2015 at the American College of Cardiology 2015 Scientific Sessions in San Diego, CA, as part of an oral session highlighting original research. The antidote has already been shown to successfully reverse the anticoagulation activity of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer).

In the second part of the ANNEXA-R study, investigators are testing the safety and effectiveness of andexanet alfa administered as an intravenous bolus followed by a continuous infusion of 8 mg/min for 120 minutes. These results are expected in the middle of 2015.

Andexanet alfa is currently being tested as an antidote to edoxaban (Savaysa, Daiichi Sankyo), the newest oral anticoagulant just approved by the US Food and Drug Administration, and the still-unavailable betrixaban (Portola Pharmaceuticals). Boehringer Ingelheim is in the process of developing an antidote specific to its own drug, dabigatran (Pradaxa), a direct thrombin inhibitor.

Currently, the FDA has designated andexanet alfa a breakthrough therapy, which is meant to help accelerate the development and review of drugs for serious or life-threatening conditions. This is awarded when early evidence suggests the agent represents a substantial improvement over existing therapies on one or more significant end points.

An antidote for the new generation of oral anticoagulants, of which none are yet available, would be welcomed by physicians for managing otherwise-uncontrolled bleeding. Bleeding related to warfarin can be reversed with low-dose vitamin K1 or a newer product, prothrombin complex concentrate (Kcentra, CSL Behring), but no such reversal agent exists for the factor Xa inhibitors or dabigatran.

[BobD Volunteer]

Thank you Iris. Now those on NOACs just need to avoid playing with sharp things till it is available over the counter over here. LOL

At present red cell packing is the only solution I understand.

Bob

[iris1205 in reply to BobD]

Like when I ran my finger through a spiral grater?

[greengo1 in reply to BobD]

While on rivaroxiban I have cut myself with razors and using saws numerous times.

Bleeding was normal and easily stopped with a plaster. I have also had operations and tooth extractions after coming off rivaroxiban for 48 hours and again no problems with bleeding.

Everyone is different but this is good news for all of us.

I understand that warfarin poses a bigger risk of INTERNAL bleeding than these new anticoagulants

Thank you for the very good news Iris

[jnh1 in reply to greengo1]

Let's not forget Warfarin has been around for 50 plus years and is tried and trusted. J.

[greengo1 in reply to jnh1]

You are correct, but let us not also forget that SOME people are intolerant to warfarin as well and so need an alternative

[iris1205 in reply to jnh1]

...and has its own complications as well. I know from experience. I was thrilled by the lack of need to control INR and was never once refused an intervention as I wasn't in a norm! We take the pluses we can with what we are prescribed!

[rosyG]

that's Great thank you- i didn't know it was already there for Apixaban- good news indeed!!

[Japaholic]

Interesting story thanks for sharing!

[Thomps95]

Thanks Iris - I didn't realize there was an antidote for apixaban. Made my day.

[Mrspat]

I wonder whether this will also be useful in situations where people have to come off an anti-coagulant temporarily e.g. before surgery? Could there be an alternative to those dreadful heparin stomach injections?

[iris1205 in reply to Mrspat]

I doubt it as it has a fairly short half life and generally we are just told to stop - if it isn't emergency surgery! I take the injections in my thigh!

[Finvola]

Thank you for the article, Iris - good news to start the day.

[jeanjeannie50]

Very interesting, thanks for letting us know this Iris. I wonder how long before this will be available. Good news.

[Offcut]

I do not want to be the devils advocate!

41 healthy volunteers treated with rivaroxaban 20 mg for 4 days? Then the antidote is dripped in the body for 2 hours to work? The fact that there is positive results can only be a good thing! But not a conclusive study.

Phases of clinical trials

Clinical trials are conducted in “phases.” Each phase has a different purpose and helps researchers answer different questions.

Phase I trials: Researchers test an experimental drug or treatment in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.

Phase II trials: The experimental drug or treatment is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.

Phase III trials: The experimental drug or treatment is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the experimental drug or treatment to be used safely.

Phase IV trials: After a drug is approved by the FDA and made available to the public, researchers track its safety, seeking more information about a drug or treatment’s risks, benefits, and optimal use.

[iris1205 in reply to Offcut]

Good point, but at least a start. Personally, when I accepted taking the Rivaroxaban, after a couple of weeks I stopped thinking about the lack of an antidote!

[jnh1]

So until further development a d approval is reached, the answer is no. J.