Blood Thinners and anti-coagulants

(3/28/19)- Bayer AG and Johnson & Johnson said they have agreed to pa $775 million to resolve claims that their blood thinner Xarelto causes excessive bleeding.

The settlement resolves about 25,000 claims and is structured to limit liability going forward. The two companies jointly developed the drug and will evenlingly split the cost of the settlement.

Xarelto is Bayer’s top selling drug and will continue to be sold. A warning label change in 2015 helped produce the settlement.

(9/7/17)- In his column in the Sept. 6 edition of the Wall Street Journal, “The News Should Get Blood Pumping, Charles Grant discusses the effectiveness  of Johnson & Johnson and Bayer’s clot preventions drug Xarelto.

“Patients who took Xarelto in combination with aspirin experienced a 24% decline in those serious events (stroke, heart attack amputation or death), compared with patients who took just aspirin. The trial was halted early.”

Dr. Pete DiBatestte, head of cardiovascular research at J&J presented the results of the study at a medical conference last month.

(10/11/16)- As we noted in our item dated 1/9/13 below, the Food and Drug Administration (FDA) approved Eloquis, a blood thinning medication from Pfizer Inc., and Bristol Myers Inc. for patients with atrial fibrillation. For those of our viewers using this medication we’d like to alert you to the “Important Safety Information” notice that appeared in the media.

The notice advised users of the drug to not taking Eliquis for atrial fibrillation before talking to your doctor who prescribed the drug, since ceasing using the drug could increase your risk of having a stroke.  The alert went on to state that “Eliquis can cause bleeding, which can be serious, and may rarely lead to death”.

Using the drug along with aspirin, NSAIDS, warfarin (coumadin), heparin, SSRIs or SNRIa, and other blood thinners may increase your risk of bleeding, and it may take longer for the bleeding to stop.

(3/25/16)- AstraZeneca PLC announced that its prescription blood thinner Brilinta was no more effective than aspirin at preventing major heart problems in stroke patients.

The British based company had hoped that the large clinical trial would open up a new area of the blood thinner market for the drug, which is already approved for patients recovering from heart attacks

(2/29/16)- As we noted in our item dated 5/25/12 below, the Federal Drug Administration’s (FDA) advisory panel had voted against approval for Johnson & Johnson’s anti-coagulant drug Xarelto, since usage of the drug could lead to excessive bleeding. The FDA however did okay the usage of the drug.

The media has recently carried the news item that the agency is now investigating whether a faulty blood-testing device may have compromised the results of a clinical trial that led to the FDA’s approval of the drug.

The agency has requested that J&J answer questions about whether there was evidence that the device was malfunctioning, according to a legal brief that was recently filed by attorneys for claimants injured by using the drug.

The attorneys for the plaintiffs alleged in their briefs that doctors had pointed out the dangers to patients who were involved in the clinical trial who were suffering excessive bleeding. The clinical trial was led by Dr. Robert M. Califf, whose nomination to head the FDA was recently approved by the Senate. The clinical trial was known as Rocket AF.

The FDA has stated it is looking into the matter, but has not put usage of the drug on hold while it investigates the issue The devise in question is known as the IN Rato device.

(1/9/13)- Although we noted in our item dated 7/3/12 below that a decision by the Food and Drug Administration for approval of Pfizer Inc. and Bristol-Myers Squibb Co,'s blood thinning medication Eliquis was not expected until March, the agency did approve the drug for sale in this country, to treat patients with atrial fibrillation.

The FDA has previously granted approval for competing drugs Pradaxa from Boehringer Ingelheim GmbH and Xarelto from Johnson & Johnson. Daichi Sankyo Co. close to applying for its blood thinning medication.

The trail study of 18,201 patients compared Eliquis to warfarin, which has been the "gold standard" as a blood thinner and clot preventer for over 50 years. Drug regulators in the European Union, Canada and Japan have previously given Eliquis their nod of approval.

Eliquis is a so-called Factor Xa inhibitor, which is the point in the blood0clotting process where it intervenes.

Although our item dated 1/13/12 below noted that Boehringer Ingelheim GmbH's blood-thinning drug Pradaxa slightly increased the risk of heart attack, another problem with usage of the drug is the fact that there is no known antidote for the drug if something goes wrong.

The drug has been linked to more than 500 deaths in the U.S., but the results of a just released report from the FDA showed that the drug did not show a higher risk of bleeding than for patients taking warfarin. When the drugs was first approved by the FDA in October 2010, proponents for the drug emphasized that it was the first replacement for coumadin or warfarin in 60 years.

Unlike warfarin, Pradaxa does not require frequent blood monitoring tests to ensure that it is working.

Praxada was identified as the primary suspect in 542 deaths reported to the FDA in 2011, and was linked to more reports of injury or death than any of the more than 800 drugs regularly monitored by the Institute for Safe Medication Practices, a nonprofit drug monitoring organization.

About 725,000 patients have used the drug since the FDA approved it in 2010, and it is a blockbuster drug for Boehringer having registered over $1 billion in sales for the company in 2011.

(7/3/12)- U.S. regulators requested more information about the clinical data used to support Bristol-Myers Squibb Co. and Pfizer Inc. application to market its new anticlotting drug Eliquis that we discussed in our item dated 3/4/12 below. The drug has been approved for usage in Europe, but this decision will delay its introduction in the U.S. for at least several months.

Once the companies reply to the FDA's request, the agency will then have up to 6 months to act on the new data. Pfizer and Bristol-Myers are seeking approval from the FDA to market Eliquis for the prevention of strokes in people with atrial fibrillation

(5/25/12)- A Federal Drug Administration advisory panel that was led by Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic voted against approval of expanding the approved usage of Johnson & Johnson's anti-coagulant Xarelto.

The drug had been approved last year to prevent blood clots in patients undergoing knee or hip replacement surgery, and for people with heart arrhythmia known as atrial fibrillation. Please see our item dated 11/17/11 below. At that time the agency had gone against the wishes of its advisory panel that had voted against approval of the drug.

Johnson was seeking approval for the prescribing of the drug on patients with acute coronary symptoms. Aspirin plus the drug clopidogel, or Plavix is the only approved drug combination for this problem. Six members of the panel voted against approval, four were in favor of approval and one panel member abstained from the voting.

The panel was concerned by the fact that dangerous bleeding occurred in some of the trial patient's brain. The majority felt that risks outweighed the benefits of the drug. The agency will consider the panel's advice but does not have to abide by it.

The panel was also concerned by the fact that over 15% of the trial patients dropped out of the study. The syndrome occurs when a blood clot blocks a coronary artery and reduces the blood supply to the heart.

(3/4/12)- The Food and Drug Administration (FDA) has delayed a decision " on Bristol-Myers Squibb Co., and Pfizer Inc., anticlotting drug Eliquis until June 28, after the companies provided new information to the agency. Please see our earlier item on Eliquis dated 12/4/11 below.

The companies stated that the supplemental information that they submitted to the agency dealt with additional information from already ongoing clinical trials of the drug. The FDA classified the additional information as a major amendment to their application, requiring additional time for review. The drug has already been approved for sale in Europe for preventing blood clots after hip- or knee-replacement surgeries.

Pfizer and Bristol-Myers are seeking approval from the FDA to market Eliquis for the prevention of strokes in people with atrial fibrillation.

The FDA had assigned "priority review" status for the drug in November, 2011, which meant the approval process was shortened to 6 months from the standard 10 months, and is reserved for proposed new drugs that could offer a major advancement in treatment.

Bristol-Myers was the original developer of the drug in 2007, and formed a partnership with Pfizer to co-develop and sell the drug.

(1/13/12)- The results of a new study of the blood thinning drug Pradaxa, which is being marketed by Boehringer Ingelheim GmbH showed that there was a slight increase in the risk of having a heart attack. According to the analysis by two Cleveland Clinic researchers which was published in a recent edition online of the Archives of Internal Medicine, Pradaxa boosted the risk of a heart attack and a condition known as acute coronary syndrome by 33%.

The analysis involved more than 30,000 patients who received either Praxada with other blood thinners such as warfarin or enoxaparin, or a placebo.

Ken Uchino, a Cleveland Clinic neurologist, the lead researcher for the study, said the actual increase in the number of heart attacks and acute coronary syndrome events was very small and was outweighed by the benefit of the drug's ability to reduce the number of strokes.

Pradaxa was approved in the U.S. in 2010 to treat atrial fibrillation, which is an irregular heartbeat that puts people at higher risk of developing blood clots. The original Pradaxa study conducted by the company that led to the FDA's approval of the drug suggested a small increased risk of heart attack with the use of the drug compared to warfarin. 

(12/4/11)- The FDA has assigned "priority review" status to Bristol-Myers Squibb Co., and Pfizer Inc., for their anticlotting drug Eliquis. A drug is given "priority" status (6 months review) when it is believed to be a drug that is superior to existing drugs or therapies, versus the normal 10 months for standard reviews of new drug applications.

The targeted date for a FDA decision is March 28, 2012. Eliquis is a drug that hopefully will prevent strokes in people with the heart-rhythm disorder known at atrial fibrillation. As noted in our item dated 11/17/11 below, the FDA recently granted approval to Johnson & Johnson and Bayer AG to market its anticlotting drug Xarelto.

Eliquis has already received European regulatory approval for the treatment of preventing certain blood clots in people undergoing knee and hip-replacement.

Several clinical trial results have shown that Eliquis significantly outperformed warfarin, Pradaxa, and Xarelto.

(11/17/11)- Going against the recommendation of its advisory panel that we discussed in our item dated 9/12/11, the Food and Drug Administration approved the anticlotting drug Xarelto from Johnson & Johnson and Bayer AG.

The drug will have a warning on its label stating, "An increased rate of stroke was observed following Xarelto discontinuation in clinical trials" in patients with atrial fibrillation.

Eric J. Topol, chief academic officer at Scripps Health in LaJolla, California stated, "This needs to be watched in the real world when it's on the market."

(9/12/11)- A Food and Drug Administration advisory panel rejected the agency's staff analysis and recommended approval of Johnson & Johnson and Bayer AG 's Xarelto for the drug's usage in connection with the prevention of strokes in people with the heart-rhythm disorder known as atrial fibrillation.

For more info on this matter, please see our item dated 7/11/11 below.

The panel's vote was 9-2 with one abstention. The FDA's staff reviewer said in a report that the comparison study with warfarin was unfair, and the researcher's study gives a misguided comparison with warfarin. The report advised against approval of Xarelto for stroke prevention.

The study included 14,264 patients in 45 countries taking either Xarelto or warfarin. The new drug will cost about $5 to $7 a day, whereas warfarin costs only pennies a day.

(9/3/11)- Researchers announced the results of their clinical trial of the anticlottinng drug apixaban (Eliquis) from Bristol-Myers Squibb Co. and Pfizer, Inc. at the meeting in Paris of the European Society of Cardiologists recently, and they were quite positive. For more information on this drug please see out item dated 6/28/11 below.

Apixaban resulted in a reduction of the risk of stroke in patients with the heartbeat irregularity called atrial fibrillation, by 21% and lowered by 31% the incidence of bleeding, which is a serious side effect of warfarin.

The pill is taken twice a day and costs about $8 a day versus the $1 a day cost for warfarin. It cut the risk of patients' death by 11% over a follow-up of nearly 2 years. Apixaban proved superior to warfarin on all three measures of efficacy, safety and survival.

The result of the study, called Aristotle which was sponsored by Pfizer and Bristol Myers was also published online by the New England Journal of Medicine. Christopher Granger, a researcher at Duke University's Duke Clinical Research Institute was the lead investigator for the study.

Johnson & Johnson and Bayer AG 's Xarelto, which we discussed in our item dated 7/11/11 below will be reviewed by an FDA panel for approval of its usage for atrial fibrillation on September 8

Apixaban is to be submitted for FDA approval later this year.

(7/11/11)- Johnson & Johnson and Bayer AG announced that the FDA had approved its oral anticoagulant drug Xarelto to prevent certain blood clots, known as venous thromboembolism, or VTE, in people undergoing knee-and hip replacement surgery. Xarelto is also known by the generic name for its active ingredient, which is rivaroxaban. To see some additional details on Xarelto, please see our item dated 11/14/10 below.

The drug has been available in Europe since 2008, but the FDA declined to approve the drug for sale in this country in 2009 because it sought additional data from the companies regarding the safety of the drug.

The companies are seeking approval in this country and in Europe to gain approval for the drug's usage in connection with the prevention of strokes in people with the heart-rhythm disorder known as atrial fibrillation.

J&J will handle marketing of the drug in this country while Bayer will deal with the marketing of the drug outside the U.S.

(6/28/11)- Warfarin has been the anticlotting drug of choice for almost 50 years now. Last year the FDA approved Pradaxa, from Boehringer Ingelheim as an anticlotting drug for the preventing blood clots and strokes, while Xarelto, from Bayer and J&J is presently under review for approval from the FDA.

Now a drug known as apixaban, or the brand name of Eliquis from Bristol-Myers Squibb Co. and Pfizer, Inc. has shown great promise according to early indications from the companies in preventing more strokes with less bleeding than does warfarin. The companies said that they planned to release the full results of the study at the European Society of Cardiology meeting in Paris on August 28th. Eliquis was approved in Europe last month to prevent clots in patients receiving hip or knee replacement surgery.

The newer drugs are expected to cost much more than warfarin, which costs pennies a day. Pradaxa cost about $6 per day.

The study compared Eliquis to warfarin in 18,201 patients with atrial fibrillation and at least one other risk factor for stroke. According to the early results that were released Eliquis was superior in preventing strokes and avoiding major bleeding than was the warfarin.

(4/6/11)- Merck & C0. announced that it is returning rights to betrixaban, a new blood thinning drug to closely held Portola Pharmaceuticals Inc. Merck had obtained those right from Portobla for $50 million in 2009. Portols said that it would continue to develop the drug without Merck.

Betrixaban is in the class of drugs called factor Xa inhibitors that are under development at several other drug companies as a replacement for the most popular blood thinners warfarin and coumadin.

As noted in our item dated 10/23/10, the Food and Drug Administration recently approved Boehringer Ingelheim GmBH's blood-thinning drug Pradaxa for sale to the public.

Please also see our item dated 9/23/10 below for other possible blood-thinning drugs now being developed by other drug companies.

(11/14/10)- Johnson & Johnson will present the results of the clinical study of its new blood-thinning drug rivaroxaban at the meeting American Heart Association on Monday. Please see our item dated 9/23/10 below for more info about the FDA's approval of Boehringer Ingelheim GmbH's blood-thinning drug Pradaxa for treatment in cases of atrial fibrillation.

The trial involved more than 14,000 patients that tested whether the drug is at least as effective as the drug warfarin in preventing stokes in people who suffer from an irregular-heart-beat condition called atrial fibrillation.

If all goes well the drug could be on the market by late 2011

The drug was co-developed by J & J along with Bayer AG of Germany, and it is hoped that it can be used to replace warfarin, which has been on the market for many years.

In addition to stroke prevention, the anti-coagulants have been tested to treat deep vein thrombosis and to prevent blood clots after hip-and knee-replacement surgery.

The rivaroxaban study is called Rocket-AF.

(10/23/10)- The Food and Drug Administration (FDA) approved Boehringer Ingelheim GmBH's blood-thinning drug Pradaxa to prevent strokes in patients with irregular heart rhythms. Please see our item dated 9/23/10 for more on this matter.

Pradaxa is a new type of anticoagulant designed to prevent the formation of blood clots. Warfarin, which is the most widely used anti-coagulant has been around since 1954.

Pradaxa (dabigatran) is approved outside the U.S. to prevent blood clots in patients undergoing knee-or-hip-replacement surgery. An FDA advisory panel recommended the approval of Pradaxa to treat atrial fibrillation.

Norman Stockbridge, the director of the FDA's cardiovascular and renal-products division stated: "Unlike warfarin, which requires patients to undergo periodic monitoring with blood test, such monitoring is not necessary for Pradaxa.

(9/23/10)- A Federal Drug Administration panel voted unanimously to recommend the approval by the agency of Boehringer Ingelheim GmbH's blood-thinning drug Pradaxa. Pradaxa and similar drugs are anticoagulants designed to prevent the formation of blood clots.

Warfarin, which is sold under the brand name of Coumadin is the "gold standard" for this type of drug, and it has been approved as an anticoagulant since 1954.

Pradaxa is also known by its generic name of dabigatran..The drug has been approved outside the U.S. to prevent blood clots in patients undergoing knee or hip replacement surgery. The panel voted 9-0 in favor of approving the drug to reduce the risk of stroke and blood clots inpatients with atrial fibrillation.

Please see our item dated 9/3/10 immediately below.

(9/3/10)- Researchers presented the results of their studies of two different anticoagulant drugs at the meeting of the European Society of cardiology in Stockholm on Tues.

One of the studies covered apixaban, under development by Bristol-Myers Squibb and Pfizer, and the other being rivaroxaban, also known as Xarelto which is made by Bayer Healthcare and Johnson & Johnson.

The FDA is currently reviewing an application from Boehringer Ingelheim for dabigatran, as a stroke prevention medication for patients with atrial fibrillation. The agency is also reviewing an application for Johnson & Johnson for rivaroxaban to be used to reduce the risk of blood clotting in patients undergoing knee or hip replacement surgery.

Rivaroxaban is already marketed for that purpose in 75 countries outside the U.S., including Canada.

According to data from IMS Health, a health care information company, pharmacies in the United States dispensed about 35.6 million prescriptions for the warfarin family of oral anticoagulant drugs.

Daiichi Sankyo's edoxaban, and betrixaban being co-developed by Merck & Co., and closely held Portola Inc. are two other promising anti-coagulant drugs in the pipeline.

(11/4/08)- Five pharmaceutical companies are presently known to be developing new treatments for blood clots. Three of the drugs are now in late phase of clinical testing. They are Bayer AG in partnership with J&J, Boehringer Ingelheim GmbH, and Pfizer Inc. in partnership with Bristol Myers-Squibb

Two of the drugs, Bayer's Xarelto and Boehringer's Pradaxa have been approved for short-term use in the European Union to prevent blood clots in patients recovering from hip-or knee-replacement surgery.

Pfizer and Bristol's Apixaban isn't yet on the market. Bayer and J&J's Xarelto is approved in Canada and is awaiting approval in the United States.

It is estimated that about 544,000 people die worldwide as a result of blood clots.

Vitamin K antagonists, such as heparin and warfarin (generic) are currently the two principal treatments for thromobisis.

Warfarin is taken in pill form, whereas heparin has to be injected. The current standard heparin therapy is Sanofi-Aventis SA's Lovenox. Warfarin is less effective if taken with certain foods, such as cranberry juice and alcohol, or with many other medications. Patients need to undergo regular lab tests to insure that they are taking the proper dosage of the medication.

Another long-term application is the prevention of more heart attacks or strokes in patients who have already had them. Presently these patients are treated with Plavix, marketed by Bristol-Myers, or aspirin. Bayer plans to present the results of a mid-stage study for this usage next month.

(2/21/06)- AstraZeneca PLC announced that it would terminate all development of its new anticoagulant drug Exanta. The announcement followed a serious case of liver damage, and would result in the termination of the clinical trial involving some 600 individual. The company also announced that it was no longer approving the usage of the drug in some 400 patients who were taking the drug for the short-term prevention of venous thromboembolism after surgery.

Sales in 2005 totaled $575,000 according to the company. At one point the company had hoped that the drug would eventually result in sales of $3 billion.

(8/07/05)- The following is the reply that we got to an email that we sent to AstraZeneca to see if we could find out what the latest developments were in regards to their anti-clotting drug Exanta-

"Thank you for contacting AstraZeneca LP regarding EXANTA® (ximelagatran).AstraZeneca announced on October 8, 2004 that the US Food and Drug Administration (FDA) did not grant approval for the investigational oral anticoagulant EXANTA. The company had submitted a New Drug Application (NDA) for EXANTA for the prevention of strokes in patients with atrial fibrillation, for the prevention of blood clots in patients undergoing knee-replacement surgery, and for the long-term secondary prevention of blood clots following standard treatment of a clot.Following receipt of this letter, the company is considering how to proceed further with the FDA.EXANTA has been approved by European regulatory authorities for the prevention of blood clots in patients undergoing hip- and knee-replacement surgery, and has been launched in seven European markets. AstraZeneca continues to believe in the benefit/risk profile of EXANTA and will work with European and other regulatory authorities towards further approvals.If we can further assist you or your health care professional, please contact the Information Center at AstraZeneca at 1-800-236-9933, Monday through Friday, 8 a.m. to 7 p.m. ET, excluding holidays."

Sincerely,Linda DiMartinoBrand SpecialistInformation Center at AstraZeneca

(9/18/04)- Approval in the US was widely anticipated but is in doubt after a key FDA panel of experts recommended rejection of Exanta over concerns about hepatotoxicity. Submissions to the FDA included use of Exanta in stroke prevention in patients with atrial fibrillation, long-term secondary prevention of VTE and prevention of VTE in total knee replacement. Analysts believe AstraZeneca may now withdraw its application to avoid a 'non approvable' letter from the FDA, and re-submit with new data in one to two years time.

 Following the review by the French Regulatory Authority (AFSSAPS) of the Exanta® regulatory submission made in December 2003 AstraZeneca today announced receipt of a request for more information before the drug can be considered for approval of long-term use in Europe.

The French authority has been acting as the Reference Member State for the European Mutual Recognition Procedure (MRP) and has been reviewing data on Exanta in the prevention of stroke and other thromboembolic complications associated with atrial fibrillation (AF, an irregular heartbeat) and the treatment of venous thromboembolism (VTE).

AFSSAPS has requested further clinical information confirming the efficacy and demonstrating safety of Exanta in AF to allow a definitive benefit/ risk assessment to be made while, for VTE treatment, the authority does not believe the data presented in the single THRIVE Treatment study provides adequate support for this use of Exanta and is proposing a rejection of this indication. AstraZeneca will now have discussions with AFSSAPS to examine what additional data needs to be generated for the AF file to be progressed further.

"Given the limitations of current therapy in the prevention of thrombosis in patients with atrial fibrillation and its potentially life threatening complications, this remains an area of great unmet need," commented Dr Hamish Cameron, Vice President, Head of Exanta, AstraZeneca. "AstraZeneca remains committed to research in this area of medicine."

In May 2004, Exanta was approved by the European regulatory authorities for the short-term indication, the prevention of blood clots in patients undergoing hip- or knee-replacement surgery. This included a commitment to perform an additional study post-approval and the protocol is currently under discussion within the EU. Exanta has since been made available in nine European countries and Argentina.

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(10/18/04)-The FDA will vote on October 22 2004 at its formal hearing whether or not it will accept the committee's recommendation in connection with Exanta. It can approve the drug even if the advisory committee voted to deny its approval of the application.

The FDA's Cardiology and Renal Advisory Committee failed to approve AstraZenaca's Exanta at its meeting on September 10th.. The big question mark in connection with Exanta is the drug's safety profile, since liver toxicity is a key matter. The advisory committee voted to tell the FDA that the potential risk to hearts and livers outweigh the benefits for patients who have had knee-replacement surgery, and for preventing new blood clots in people being treated for one.

Earlier this year, European regulators approved Exanta for use in knee-replacement operations and for patients who were suffering from blood clots in their legs. Patients using the drug for knee surgery would be on the drug for 12 days. The company is also proposing that the drug be used for longer-term use in patients with atrial fibrillation, or irregular heartbeat, since this problem can cause fatal blood clots. The company also claims that the drug can be used as a secondary treatment for patients with deep vein thrombosis, or blood clots in the legs.

Dr. Hamish Cameron, an AstraZeneca vice president overseeing Exanta, said the benefit of the drug is that a standard, single dose can be administered and that patients would not face any dietary restrictions. Patients using the drug on a short-term basis would not have to be monitored. Dr. Cameron went on to state that patients using the drug on a long term basis would have to be monitored on a monthly basis for possible damage to the liver. The advisory committee however said that monthly monitoring is not sufficient and that a patient registry should be established by the company which would "restrict distribution measures to limit population risk."

The committee also found that its review of the clinical data for patients using Exanta for 12 days, or short term use, suggested a higher risk of adverse coronary events such as heart attacks, and that bleeding events were higher in Exanta patients compared to Warfarin patients.

The results for SPORTIF V were announced in November of 2003. 3,922 patients were enrolled and followed from 1 to 2 years. This study was a double blind study, meaning neither patient nof treating physician knew which medication was given to the patient. Patients on the study drug still had their INR measured (the value to determine proper dosing of coumadin). A computer program generated faxed data that would force the physician to make adjustments from time to time as if the patient was on regular coumadin. Exanta® was associated with fewer strokes and systemic emboli (though not statistically significant) and less bleeding (statistically significant) than those patients who were on Coumadin.  

If approved by the FDA and European regulators, AstraZeneca's new blood thinning medication Exanta (ximelagatran) will be the first new drug to hit the market to deal with anticoagulation in almost 60 years. AstraZeneca hopes for approval of the NDA by the end of 2004.

The results of a study of Exanata TM (ximelagatran) as an effective and convenient replacement for warfarin for prevention of stroke in atrial
fibrillation was announced at the 52nd Scientific Session of the American College of Cardiology (ACC) in Chicago in April 2003. Results of the SPORTIF III, a multi-national, randomized study suggest that Exanta can offer great improvement in preventing stroke in patients with atrial fibrillation. The study also supported the emerging benefit-risk profile of Exanta.

The primary endpoint was met, showing that a fixed dose taken twice a day of 36mg oral Exanta compared favorably with dose-adjusted warfarin in
preventing stroke and systemic embolic events in atrial fibrillation. In the SPORTIF III trial, the incidence of liver enzyme (ALT) elevations was
6.5% for Exanta, and mostly occurred within the first 6-months of treatment. Levels returned back to normal shortly after the six month period of time. The combined rate of major and minor bleeding events was found to be significantly lower for Exanta than warfarin (475 vs 455 events; p=0.007) and there was no significant difference in all cause mortality between the

Warfarin has been around for over 50 years but it requires constant monitoring and dosing adjustments to keep the blood from clotting or getting too thin. Another negative side effect that has plagued warfarin is that it reacts with many drugs and food. Atrial fibrillation effects some two million Americans a year, and is associated with a five-fold increase in the risk of stroke. It is estimated that atrial fibrillation accounts for about 15% of all strokes worldwide.

Exanta is the first of a new class of drugs called direct thrombin inhibitors. One of the negative side effects associated with the drug is that it was associated with elevated liver enzymes in about 6% of patients. While this effect was only transient, it will mean that patients will have to be closely monitored for about 6 months. The drug does however eliminate the need for constant dosing adjustment.

Astra plans to submit the drug for approval by the FDA and European authorities by year's end. We must however caution that Astra sponsored the study. In the study 7,329 patients were randomly assigned to either Exanta or warfarin, and were treated for an average of 20 months. Even though 51 of the Exanta patients suffered from a stroke or other serious clotting episode, as compared to 37 of the coumadin patients, the findings were not considered statistically significant.

Since warfarin is a generic drug it is inexpensive, but because of the added expense that could be eliminated if close monitoring of the patient is eliminated, the long run saving to the medical system could be substantial.


Allan Rubin
updated March 28, 2019

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