Pradaxa

[BLADEMDA]

UPDATE: Boehringer's Blood-Thinner May Edge Out Bayer's

August 28, 2009: 11:04 AM ET

​

(Adds detail on who makes Warfarin.)
By Allison Connolly
OF DOW JONES NEWSWIRES
FRANKFURT -(Dow Jones)- German pharmaceutical company Boehringer Ingelheim is set to unveil much anticipated results from a pivotal clinical trial of its blood thinner Pradaxa, setting the stage for a showdown with German rival Bayer AG's (BAY.XE) competing drug Xarelto.
Both are seen as blockbuster drugs - with potential to earn the companies more than EUR1 billion each in peak sales. While both drugs are approved for short- term use in Europe, the holy grail they are competing for is approval for use in chronic conditions such as stroke prevention, which would mean steady streams of revenue.
Privately-owned Boehringer Ingelheim will present the results of its stroke prevention study on Sunday afternoon at the European Society of Cardiology in Barcelona. The RE-LY study compares patients with atrial fibrillation, a common heart rhythm disorder, on Pradaxa against those on the industry standard warfarin.
Commerzbank analyst Daniel Wendorff said a comparable study from Bayer isn't expected until the second quarter of 2010, so the Pradaxa study could be telling.
"If the data looks good then Pradaxa gets the advantage," Wendorff said.
But if the results don't meet expectations, Bayer would have time to play catch up to Boehringer's lead of around a year.
Warfarin, best known by its brand name Coumadin, has been widely prescribed for about 50 years. Its only competition has been heparin and Sanofi-Aventis' ( SNY) Lovenox, both of which must be injected. Coumadin is made by Bristol-Myers Squibb Co. (BMY), while generic versions are made by companies including Teva Pharmaceutical Industries Ltd.'s (TEVA) Barr Pharmaceuticals Inc., Novartis AG's (NOVN.VX) Sandoz, Upsher-Smith Laboratories Inc. and Cadila Healthcare's unit Zydus Pharmaceuticals (USA) Inc.
Analysts say the first of the new generation of oral anticoagulants to make it to market have the potential to snare the lion's share from warfarin, so they are keen to see how Pradaxa fared in the study.
"It will probably have an effect on Bayer because Xarelto is its most important competitive drug," said Merck Finck & Co. analyst Carsten Kunold.
A Bayer spokeswoman declined to comment on Boehringer's upcoming results.
Wendorff estimates that Bayer has the potential to earn EUR2.2 billion in peak sales from Xarelto, of which EUR550 million would come from stroke prevention in patients with irregular heartbeats.
Both Xarelto and Pradaxa have been approved in Europe for the prevention of blood clots after total hip and knee replacements.
Other competitors farther behind in development include apixaban, being developed by Pfizer (PFE) and Bristol-Myers Squibb (BMY), and betrixaban from Merck & Co. (MRK)
Bayer and its U.S. marketing partner Johnson & Johnson (JNJ) have had some trouble getting swift U.S. approval for Xarelto from the Food and Drug Administration.
In May, the FDA declined to approve the treatment, saying that it needed more data, although it didn't ask for further clinical or non-clinical testing of the drug. Bayer said it would file a full response letter to the regulator, but not before the fourth quarter at the earliest.
Both good and bad news from the Pradaxa study on Sunday could hurt Bayer shares Monday, Merck Finck analyst Kunold said. Because the two drugs are so similar, Kunold said the market could interpret good results to mean Pradaxa is superior to Xarelto, while negative news about side effects could also read across to Xarelto.
Morgan Stanley analysts wrote in a note that Pradaxa may appear superior to Xarelto based on the way the RE-LY trial was designed. More than half of Boerhinger's test group were patients who had never received warfarin previously, Morgan Stanley said.
The brokerage points out that results from another warfarin trial published in The Lancet in 2006 showed patients who hadn't taken warfarin previously experienced more side effects when taking the drug for the first time compared with those who had taken it before.
Boehringer said it included first-time warfarin patients in the study for a sub-analysis and will present those findings at the conference on Wednesday.
-By Allison Connolly, Frankfurt Bureau; +49 69 29725513, allison.connolly@ dowjones.com

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[humblern]

got money in it or what?

 

[bigdan]

...I wish I had money in it.

dc

 

[BLADEMDA]

got money in it or what?

Idiot, this is an entire new class of P.O. blood thinners that will likely replace Lovenox I.M. injections for total joint patients. Hence, we need to be aware of the drugs, their names, mechanism of action and half-lives.

Blade

 

[herewegoagain21]

So you post a company release with no clinical information, nice very helpful I am sure you will base your anesthetic managment on this....idiot.

and as well in this commercial release is a replacmet for coumadin, at least your reply could have a little accuracy.....idiot.

 

[pgg]

So you post a company release with no clinical information, nice very helpful I am sure you will base your anesthetic managment on this....idiot.

and as well in this commercial release is a replacmet for coumadin, at least your reply could have a little accuracy.....idiot.

So this guy is clearly a tool and I don't object to him being banned after this first-ever crappy post, but his point is not entirely without merit.

Idiot, this is an entire new class of P.O. blood thinners that will likely replace Lovenox I.M. injections for total joint patients. Hence, we need to be aware of the drugs, their names, mechanism of action and half-lives.

a) You were the first to fling about the term idiot.

b) You didn't post anything about the drug's mechanism of action or half life. It was a news wire / market ticker kind of media report containing only speculation on potential profits and drug company competition. I don't think it was unreasonable at all to think you were starting a thread about the drug company's stock or investing.

No need to get so defensive.

 

[BLADEMDA]

European Medicines Agency Recommends Approval Of Novel Oral Anticoagulant, Dabigatran Etexilate (Pradaxa®)

Main Category: Cardiovascular / Cardiology
Also Included In: Regulatory Affairs / Drug Approvals; Clinical Trials / Drug Trials; Pharma Industry / Biotech Industry
Article Date: 03 Feb 2008 - 0:00 PDT

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Boehringer Ingelheim announced that the Committee for Medicinal Products in Human Use (CHMP) of the European Medicines Agency has issued a positive opinion to recommend marketing authorisation of their novel, oral direct thrombin inhibitor, dabigatran etexilate. The CHMP recommends approval of dabigatran etexilate for the prevention of venous thromboembolic events in patients who have undergone total hip replacement surgery or total knee replacement surgery.1

The positive opinion is a recommendation to the European Commission that authorization to market the drug should be granted in the European Union which normally occurs within 67 days. Dabigatran etexilate will be marketed by Boehringer Ingelheim exclusively under the brand name Pradaxa®, with a planned launch in all 27 countries of the European Union.

Dr Andreas Barner, Member of the Board of Boehringer Ingelheim and responsible for Research, Development and Medicine said "We welcome the positive opinion of the EMEA which is the first recommendation for approval by a regulatory authority for our novel oral anticoagulant drug Pradaxa®. This announcement represents a major milestone in the advancement of anticoagulation therapy for thromboembolic diseases. We are pleased that our new oral thrombin inhibitor offers the potential for physicians to ensure that patients in need receive effective and safe thromboprophylaxis."

Patients who have undergone total hip or knee replacement are at high risk of venous thromboembolism (VTE). This risk extends beyond the usual period of hospitalisation, as thromboprophylaxis treatment is often discontinued following discharge due to the complex administration of current anticoagulants.2 As dabigatran etexilate is given as a fixed oral dose, it can be administered conveniently both in and out of the hospital setting, providing patients with effective protection from potentially dangerous thrombi (blood clots).

Dabigatran etexilate has a rapid onset and offset of action and predictable anticoagulation effect, without the need for coagulation monitoring. It specifically and reversibly inhibits thrombin, the central and essential enzyme in the coagulation cascade responsible for thrombus formation. Dabigatran etexilate exhibits no drug-food interactions and has a low potential for drug-drug interactions.3,4

Clinical data from the RE-NOVATETM and RE-MODELTM trials were included in the submission to European authorities in February 2007 for the first intended license indication for dabigatran etexilate. Oral, once daily administration of both 150 or 220 mg dabigatran etexilate was demonstrated to be as effective and safe as injectable enoxaparin (40mg) in preventing VTE and all cause mortality following total hip replacement surgery and following total knee replacement surgery in the RE-NOVATETM and RE-MODELTM trials respectively.5,6 All test results were evaluated by a central adjudication committee that was blinded to the treatment received by any patient.

Anticoagulation-related bleeding is the primary safety concern during hip or knee replacement surgery, since major bleeding into the replaced joint can have a detrimental impact on clinical outcome.5 In both trials, few major bleeding events (including those occurring at the surgical site) were reported and incidence did not differ significantly between dabigatran etexilate and enoxaparin treatment groups (during the RE-NOVATETM trial, major bleeding events occurred at 2.0% and 1.3% for dabigatran etexilate 220 mg and 150mg groups versus 1.6% for enoxaparin and during the RE-MODELTM trial, major bleeding events occurred at 1.5% and 1.3% for dabigatran etexilate 220 mg and 150mg groups versus 1.3% for enoxaparin).5,6

In all phase III trials reported to date, patients were frequently monitored and assessed for liver enzyme elevations by an independent data safety monitoring committee. Liver enzyme aminotransferase (ALT) elevations greater than three time the upper limit of normal (ULN) were low throughout the entire treatment periods with dabigatran etexilate and did not differ significantly between the treatment groups.

Similarly, the incidence of acute coronary events was low, particularly in the three month follow up period, with no significant differences between all treatment groups.

Boehringer Ingelheim continues to evaluate the efficacy and safety of dabigatran etexilate in a range of thromboembolic disease conditions. RE-VOLUTION™ is an extensive clinical trial programme involving more than 34,000 patients worldwide. Recent progress announcements include the early enrolment completion of 18,114 patients in the landmark RE-LY™ trial to evaluate the efficacy and safety of dabigatran etexilate for stroke prevention in patients with atrial fibrillation. Other ongoing studies are evaluating the efficacy and safety of dabigatran etexilate in the treatment of acute VTE, the secondary prevention of VTE and acute coronary syndromes.

 

[BLADEMDA]

European approval of Pradaxa® follows the submission of efficacy and safety data in February 2007 from the phase III RE-NOVATE™ and RE-MODEL™ studies.5,6 Oral, once daily administration of both 150 and 220 mg Pradaxa® was demonstrated to be as effective and safe as injectable enoxaparin (40 mg) in preventing VTE and all cause mortality following total hip replacement surgery and total knee replacement surgery in the RE-NOVATE™ and RE-MODEL™ trials, respectively.5,6 All test results were evaluated by an independent central adjudication committee blinded to the drug received by any patient.

With all anticoagulant agents it is important to optimize the balance of efficacy and safety. In addition to the critically important bleeding profile, hepatic and cardiac safety need to be considered, as well as tolerability. In both the RE-NOVATE™ and RE-MODEL™ trials, a low incidence and severity of major bleeding (including those occurring at the surgical site), similar to enoxaparin was reported.5,6

Patients were frequently monitored and assessed for liver enzyme elevations by an independent data safety monitoring committee. Rates of liver enzyme alanine aminotransferase (ALT) elevations greater than three times the upper limit of normal (3x ULN) were low and comparable to enoxaparin at any time post-baseline with Pradaxa®, supporting hepatic safety.5,6

Pradaxa® displayed a favourable cardiac safety profile; no incidences of adjudicated Acute Coronary Syndrome (ACS) events were reported during 3 months follow up with Pradaxa 220 mg, suggesting no rebound coagulation effect once treatment ends.5,6 A favourable tolerability profile, comparable to enoxaparin, was also reported following a low number of adverse events leading to treatment discontinuation.5,6

The standard recommended dosage of Pradaxa® is a fixed oral dose of 220 mg given once daily. A single capsule of 110 mg (half-dose) is administered orally between 1 and 4 hours following surgery, continuing with 2 capsules once daily thereafter for a total of 10 days in total knee replacement patients and 28-35 days in total hip replacement patients. A second approved dosage of 150 mg taken as two capsules of 75 mg is recommended for specific patient populations, including patients over 75 years of age and those with moderate renal impairment.

 

[BLADEMDA]

Here are some interesting facts about Pradaxa:

1. 220 mg dosage per day more effective at reducing DVT than Lovenox

2. 85% excreted in the Urine

3. Half life is 12-14 hours in healthy volunteers; 14-17 hour half life observed in orthopedic surgical patients.

4. Absorbed quicky into the blood stream on POD#2 at around 2 hours. When given immediately postoperatively the absorption is around 6 hours.

5. Amiodarone significantly reduces drug requirement by 50%. Hence, only 150 mg po per day required if patient on Amiodarone

6. At the rec. dosage of 220 mg per day (normal renal function, non-elderly) the risk of bleeding is increased compared to Lovenox (1.8% vs. 1.5%).


The drug is likely to receive U.S. FDA approval next year.

 

[BLADEMDA]

So you post a company release with no clinical information, nice very helpful I am sure you will base your anesthetic managment on this....idiot.

and as well in this commercial release is a replacmet for coumadin, at least your reply could have a little accuracy.....idiot.

The Trolls are here again. time for troll spray.

 

[BLADEMDA]

got money in it or what?

Troll removal system:

 

[hereiamagain2]

Are you supporting the idea of violence against those who verbally disagree with you?

 

[Arch Guillotti]

 

[GoodmanBrown]

This forum is out of control sometimes. I'm not surprised readership is dropping. I saw it coming a couple months before Obama got elected.

 

[core0]

Are you supporting the idea of violence against those who verbally disagree with you?

No he supports using pretend internet violence against someone who has no useful opinion. Re in the image of old school Venty and Jet:
http://forums.studentdoctor.net/showthread.php?t=409419&highlight=troll

 

[onceagaininthef]

As posted earlier major overcompensation.

 

[BLADEMDA]

As posted earlier major overcompensation.

You, the spammer who refuses to stop posting on SDN under MULTIPLE accounts, are talking about overcompensation?🙄

 

[GoodmanBrown]

Who keeps banning that guy? It's ridiculous that one thought that you don't appreciate is enough to get someone banned. The Anesthesiology forum has become the North Korea of SDN.

 

[Southpaw]

Who keeps banning that guy? It's ridiculous that one thought that you don't appreciate is enough to get someone banned. The Anesthesiology forum has become the North Korea of SDN.

actually banning return trolls has been commonplace all over SDN as long as I've been a member.

 

[GoodmanBrown]

actually banning return trolls has been commonplace all over SDN as long as I've been a member.

Fair enough, I understand and even agree with that policy. But, the original post that got the person in trouble was a legitimate question. Blade originally posted a news article that's basically a business memo about the drug. Not a ton of clinical information there. When the poster questioned the rationale behind the posting (in an admittedly aggressive fashion), Blade responded with a personal insult. But it was the other guy who got banned. Banning trolls is not the issue; it's the rapid categorization of someone as a troll when they post something that the regulars don't like. In my opinion, none of the person's responses has been "ban worthy," though he does stoop to the level of calling names. All the same, he's been banned three times. He could post again saying, "I love everyone on this forum." and be banned again, though it would be totally unjustified. That's my beef with this thread and this forum.

 

[Arch Guillotti]

Dude what rock did you crawl out from under?

Seriously, though you really have no idea what you are talking about. The reason for the ban had nothing to do with the post but rather because the user was a known TROLL who has been banned MULTIPLE times in the past. Once you are banned it is all over, there is no coming back. A return after a previous ban results in another immediate ban.

If you read this board regularly you should know that rather than a North Korean style dictatorship, quite the opposite is true. Several users that posted some very contradictory (and inflammatory) views were allowed to stay around because they never overtly did anything ban worthy (though many would argue otherwise). I feel that the best moderation of this board is to do as little as possible because forum members are pretty good about self moderation and letting things settle out on their own. But I do ban obvious TROLLS as soon as I see them.

Best wishes

Fair enough, I understand and even agree with that policy. But, the original post that got the person in trouble was a legitimate question. Blade originally posted a news article that's basically a business memo about the drug. Not a ton of clinical information there. When the poster questioned the rationale behind the posting (in an admittedly aggressive fashion), Blade responded with a personal insult. But it was the other guy who got banned. Banning trolls is not the issue; it's the rapid categorization of someone as a troll when they post something that the regulars don't like. In my opinion, none of the person's responses has been "ban worthy," though he does stoop to the level of calling names. All the same, he's been banned three times. He could post again saying, "I love everyone on this forum." and be banned again, though it would be totally unjustified. That's my beef with this thread and this forum.

 

[Southpaw]

Fair enough, I understand and even agree with that policy. But, the original post that got the person in trouble was a legitimate question. Blade originally posted a news article that's basically a business memo about the drug. Not a ton of clinical information there. When the poster questioned the rationale behind the posting (in an admittedly aggressive fashion), Blade responded with a personal insult. But it was the other guy who got banned. Banning trolls is not the issue; it's the rapid categorization of someone as a troll when they post something that the regulars don't like. In my opinion, none of the person's responses has been "ban worthy," though he does stoop to the level of calling names. All the same, he's been banned three times. He could post again saying, "I love everyone on this forum." and be banned again, though it would be totally unjustified. That's my beef with this thread and this forum.

Not that I'm trying to guess anyone's motives, but I think this particular user was banned a day or two ago for trolling in the midlevel forums. I think his returning 3 times in the same thread with the intention to antagonize Blade and other users rather than participate in what I would assume Blade intended as a clinical thread, was enough for the mods to conclude his only intention was to troll a little more. Just my guess though.

 

[GoodmanBrown]

Not that I'm trying to guess anyone's motives, but I think this particular user was banned a day or two ago for trolling in the midlevel forums. I think his returning 3 times in the same thread with the intention to antagonize Blade and other users rather than participate in what I would assume Blade intended as a clinical thread, was enough for the mods to conclude his only intention was to troll a little more. Just my guess though.

Fair enough. I rescind some of my more strident comments. Question, how do the mods know it was the same person? Likely it was, but just curious because just by reading "humblern"'s post, I still would not have banned him.

At Arch, I'm not sure what you mean by "What rock did you crawl out from under?" I think it's a bit much to expect anyone who posts to have read and be current with every post in the Anesthesiology forum and its subforums. I called it like I saw it and was probably wrong this time. My bad. However, I have posted in the Anesthesiology forum a number of times before and have been a reader of the forum for over a year, so I'm not just swooping in from nowhere.

 

[onemoretime50]

Dude what rock did you crawl out from under?

Seriously, though you really have no idea what you are talking about. The reason for the ban had nothing to do with the post but rather because the user was a known TROLL who has been banned MULTIPLE times in the past. Once you are banned it is all over, there is no coming back. A return after a previous ban results in another immediate ban.

If you read this board regularly you should know that rather than a North Korean style dictatorship, quite the opposite is true. Several users that posted some very contradictory (and inflammatory) views were allowed to stay around because they never overtly did anything ban worthy (though many would argue otherwise). I feel that the best moderation of this board is to do as little as possible because forum members are pretty good about self moderation and letting things settle out on their own. But I do ban obvious TROLLS as soon as I see them.

Best wishes

Dude you ban CRNA's, as you wrote once "be careful or suffer the consequenced I have a low tolerence for CRNA's" At least be upfront about your bias.

 

[UTKB]

Why won't you gooo awaaaay.👎sleep:

 

[Arch Guillotti]

Dude you ban CRNA's, as you wrote once "be careful or suffer the consequenced I have a low tolerence for CRNA's" At least be upfront about your bias.

OK I am biased

 

[OneFellSwoop]

Thought I would resurrect this de-evolved dinosaur and attempt to get it back on track since there is new FDA approval http://www.boehringer-ingelheim.com...releases/2010/20_october_2010_dabigatran.html for non-valvular A-fib, we'll start seeing this medication in patients prior to surgery. Just wondering what everyone's thoughts are for reversal/cessation prior to surgery as there isn't an antidote and the half-life approaches 17h which is about 3.5 days for full metabolism.

 

[periopdoc]

Unfortunately Boehringer Ingelheim is a privately held family company. So none of us can make any significant money off of this one.

- pod

 

[periopdoc]

In all seriousness though, I believe that this drug is quickly going to gain widespread acceptance for both on and off label use so we need to be ready to manage it perioperatively.

It is a direct thrombin inhibitor (think hirudin, lepirudin etc but with a much longer half-life than either of those).

There is no formal mechanism for reversal.

Have you ever done a pump case with DTIs? I have, and they bleed like stink.

A little nervous yet?

Options for emergent reversal include Novo-7 and Prothrombin Complex concentrates. I wonder if there will be a role for dialysis as we have been successful with ultrafiltration of lepirudin before.

Here is a great document to look over. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. van Ryn et al. Thrombosis and Haemostasis 103.6/2010


- pod