ALCapshaw2
Well-known member
A friend forwarded the following newspaper article to me. My reply is appended at the end. 'AL Capshaw'
................................................
AstraZeneca counts on new drug
Exanta could reach millions at risk of clots and stroke
By TED GRIFFITH
The News Journal
08/29/2004
For William McCool, it's been a rough summer. In June, the 68-year-old insurance broker underwent surgery to repair his heart valves, after which he developed pneumonia. Then he needed surgery again, this time to have a pacemaker implanted. But most terrifying was the internal bleeding he developed late last month. "I felt like I was burning all over," recalled McCool, who lives in Elkton, Md. The culprit for the life-threatening bleeding, McCool's doctors determined, was one of his medications, warfarin, also known by the brand name Coumadin. "This drug is nasty stuff, I'll tell you," McCool said. "You've got to be very careful with it. But unless something else comes along, I'm going to be on it for the rest of my life." If pharmaceutical company AstraZeneca gets its way, something else will soon come along for the 3 million Americans who take warfarin to prevent blood clots that can kill. AstraZeneca, which has its U.S. headquarters in Fairfax, has developed what the company describes as a superior alternative to warfarin. Executives say the new drug, called Exanta, works just as well as warfarin in preventing blood clots. But unlike warfarin, Exanta doesn't require regular testing to ensure a patient is getting the right dose. "It's the first oral treatment in half a century for the prevention of deadly and disabling strokes," said Adele Gulfo, a top AstraZeneca executive in the company's Fairfax office. For AstraZeneca, Exanta represents a linchpin in the company's strategy for increasing sales and profits through the rest of the decade. The company, which has about 4,800 employees in Delaware, is counting on Exanta and a handful of other newer prescription drugs to make up for flagging sales of older products. Company executives won't disclose revenue projections for Exanta, but some analysts estimate sales of the drug could reach $3 billion. "Exanta is the next big thing for these guys," said Susan Cross, a pharmaceutical analyst with Wilmington Trust. Finding balance Prescribing warfarin is a balancing act for doctors because its effects are unpredictable, making regular blood testing necessary. Some patients need to vary doses daily to make sure they're getting just the right amount. Too much warfarin and the patient is at risk for bleeding, too little and the patient is at risk of having a stroke caused a blood clot. Safety problems notwithstanding, warfarin also saves lives preventing strokes - a fact that's undisputed even AstraZeneca. Commonly referred to as a blood thinner, warfarin works inhibiting coagulation, the medical term for blood clotting. Clinical trial results showed warfarin could cut the risk of stroke up to 86 percent among patients with irregular heartbeat, a condition that makes a person susceptible to stroke. But the prescribing information for warfarin also warns of the risk of a "fatal" hemorrhage and urges doctors to monitor patients on the drug closely. A spokeswoman for Bristol-Myers Squibb, which markets Coumadin, declined to comment for this article. In contrast with its older rival, Exanta won't require dose adjustments. And the new pill doesn't have warfarin's tendency to interact badly with other medications and certain types of food, said Gulfo, who is responsible for overseeing sales and development of AstraZeneca's cardiovascular medicines in the United States. Although it has advantages over warfarin, Exanta has shortcomings as well, including bleeding risk. Clinical testing results also raised questions about the possibility that Exanta damages the liver. And before American patients can start taking the drug, AstraZeneca will need to persuade regulators at the U.S. Food and Drug Administration that the potential risk for liver damage is more than offset Exanta's benefits. AstraZeneca, which has its world headquarters in London, hopes to begin selling Exanta in the United States early next year. The prescription drug already is available in Germany, and the company expects to introduce Exanta in other European countries later this year. FDA to rule As a matter of policy, FDA officials won't comment publicly on upcoming decisions. But AstraZeneca will soon get a clear indication of Exanta's chances for approval. A panel of medical experts is scheduled to meet Sept. 10 to review AstraZeneca's application and make a recommendation on whether the FDA should approve Exanta. The federal agency isn't obligated to follow the recommendation of an advisory panel, but it typically does. Exanta's effect on the liver is sure to be a focus of discussion at the advisory panel meeting. In clinical testing conducted AstraZeneca, about 6 percent of patients experienced an elevation in enzymes produced the liver. Such an elevation can sometimes be a warning sign that a patient is headed for liver failure. In the case of Exanta, however, the elevation seems to be temporary and doesn't appear to lead to lasting liver damage, said Sir Tom McKillop, chief executive of AstraZeneca. Still, McKillop said the potential for serious liver damage couldn't be ruled out, and he said patients receiving Exanta will need to be watched for signs of problems. "The demand in the marketplace from patients and physicians for Exanta will be very considerable, but we need to be very disciplined in how we launch this product, so that nobody runs an undue risk," McKillop said in a telephone interview. If the FDA approves Exanta, AstraZeneca expects that the agency will require blood testing to monitor patients for elevated liver enzymes. AstraZeneca executives also acknowledged that the FDA may insist Exanta carry a so-called black-box warning - the strongest type of warning - to alert doctors to the potential risk of liver problems. Some Wall Street analysts have speculated that the FDA may initially limit Exanta to short-term use in patients undergoing orthopedic surgery, which has a high potential for causing blood clots. But AstraZeneca sees a greater market opportunity in the drug's long-term use, especially in patients with irregular heartbeat, which increases the risk of stroke fivefold. About 2.2 million U.S. patients have irregular heartbeat, known medically as atrial fibrillation. A new drug, especially one with questions about its safety, can have trouble competing against established rival drugs. But Exanta likely won't have as much trouble winning converts because it will go up against a rival known for its safety risk and inconvenient dosing, analysts said. In the words of Merrill Lynch pharmaceutical analyst James Culverwell, the alternative to Exanta is "rat poison." Rat poison saves lives Warfarin, which grew out of research in the 1930s scientists at the University of Wisconsin, was indeed first used commercially as a rat poison. And warfarin, which causes rats to bleed to death, remains the most widely used rat poison in the world, according to the Wisconsin Alumni Research Foundation. But scientists also determined that warfarin's anti-clotting properties could ward off strokes. And in 1954, the drug was introduced in the United States under the brand name Coumadin. The drug was originally marketed Endo Laboratories, which was acquired in 1969 Wilmington-based DuPont Co. DuPont sold Coumadin up until 2001 when it sold its pharmaceutical business to New York-based Bristol-Myers Squibb. Warfarin was the seventh most prescribed cardiovascular medication in the United States last year. Despite its safety risks, warfarin remains widely prescribed because, doctors say, nothing can match its effectiveness at preventing the blood clots that cause strokes. Strokes, which occur when a clot blocks the flow of blood to the brain, are the third leading cause of death in the United States and the leading cause of disability in adults, according to the American Heart Association. The likelihood of stroke increases with age. "Using warfarin is a double-edged sword, but it has been shown clearly to reduce the chances of a stroke," said Edward Goldenberg, one of McCool's doctors and a cardiologist with Cardiology Consultants, which has offices throughout Delaware. Even after he suffered the internal bleeding in late July, McCool said he never considered dropping warfarin because he didn't want to run the risk of a stroke. Immediately after he suffered the bleeding episode, McCool's doctors ordered daily testing to ensure he was getting the right dose of warfarin. Doctors only recently scaled the testing back to once a week for McCool, who runs an insurance agency with his son in Elkton. On top of the testing, McCool has to watch his diet closely. Lettuce and other leafy green vegetables can play havoc with warfarin's effectiveness because they contain vitamin K, which promotes blood clotting. Warfarin works blocking the liver's use of vitamin K. 20 years to develop AstraZeneca's quest to develop an alternative to warfarin began 20 years ago at a company lab in Molndal, Sweden. After years of trial and error, company scientists developed an experimental compound that appeared to achieve the same level of anti-clotting as warfarin but without the inconvenient testing and dietary restrictions. The compound, later called Exanta, works interfering with thrombin, an enzyme that plays a key role in blood coagulation. AstraZeneca launched a series of clinical tests to evaluate the safety and effectiveness of Exanta. The drug was tested in 17,000 patients in 30 countries. Dr. Jonathan Halperin, a professor at the Mount Sinai School of Medicine in New York, said two major company-sponsored trials he supervised demonstrated that Exanta was as good as warfarin in preventing blood clotting. Exanta also carried less risk of bleeding and a lower potential for food and drug interactions, Halperin said. He added, though, that questions persist about the effect on the liver. Gulfo, the AstraZeneca executive, conceded that patients on Exanta will need to undergo blood testing to monitor the functioning of their livers, but their dosage won't have to be constantly adjusted.The small percentage of patients who experience signs of liver trouble can stop taking Exanta and go back on warfarin, she said. McCool is eagerly awaiting the FDA's decision. He said he would welcome any drug that could free him from warfarin. "If this new drug gets approved and becomes available, you can believe I'll be talking to my doctor, and I won't wait," McCool said. "If it does turn out to really be better, I'd want to jump on it right away. I know better than most the dangers and problems with Coumadin." Contact Ted Griffith at 324-2880 or [email protected].
END of News Article
.............................
Response to friend from 'AL Capshaw':
Thanks for the interesting article Don.
As usual, the alarmist media over exagerates the risks and problems with Coumadin / Warfarin (yes, it is 'rat poison'). Unfortunately, its effects are highly dependent on Vitamin K levels and drug interactions so care must be taken when changes in medication or diet occur. Consistency in diet and medication is the key to successful regulation.
On the other hand, with PROPER monitoring and understanding of 'reasonable' variation limits, it can be managed by most people. DAILY testing tells me that the Doctor in the article doesn't know how to properly manage Coumadin. It takes 3 to 4 days for a change in dose to 'settle out' so daily tests and dosing changes GUARANTEE that the patient's INR (a measure of clotting time) will go on a roller coaster ride. A GOOD Coumadin Clinic would know how to manage their patients much better than the doctor in the article! Testing (and dose changes) should NEVER be done more often than every 3 or 4 days in the worst cases. For most patients who are experiencing 'symptoms' testing once a week is usually the preferred course, then every two weeks, and finally every 4 to 6 weeks as the patient's INR stabilizes. Home testing is the latest craze. It is common in Germany and slowing gaining acceptance in the U.S. There are 3 or 4 companies that manufacture testing instruments that are approved for home use.
The most likely scenario for Exanta will be limited approval for surgeries as indicated in the article, then the lucrative 'Atrial Fibrilation' market, and finally for Valve Replacement patients.
I noticed the author never got around to COST. You can bet the cost of a NEW Patented anti-coagulation drug is going to be VERY HIGH and probably not covered by many (most?) insurance policies. My drug coverage policy will only pay for GENERIC (Warfarin). If I want to go with the Brand Name Coumadin, I have to pay the difference which is not insignificant. Fortunately, my mail order drug company uses an Israeli made generic warfarin that is well respected and can easily be split by hand (not the case for Coumadin). I experienced NO changes in INR following the switch over.
EXANTA is a welcome addition to the anti-coagulation scene, but I expect it will be MANY more years before it becomes the defacto standard or affordable by most patients.
Al Lodwick, R.Ph. and Coumadin Clinic Director in Colorado has a very informative website at www.warfarinfo.com which addresses just about everything anyone would ever want / need to know about warfarin / Coumadin, including Exanta and it's approval status.
'AL Capshaw' (Coumadin / warfarin user for over 2 years with stable INR)
................................................
AstraZeneca counts on new drug
Exanta could reach millions at risk of clots and stroke
By TED GRIFFITH
The News Journal
08/29/2004
For William McCool, it's been a rough summer. In June, the 68-year-old insurance broker underwent surgery to repair his heart valves, after which he developed pneumonia. Then he needed surgery again, this time to have a pacemaker implanted. But most terrifying was the internal bleeding he developed late last month. "I felt like I was burning all over," recalled McCool, who lives in Elkton, Md. The culprit for the life-threatening bleeding, McCool's doctors determined, was one of his medications, warfarin, also known by the brand name Coumadin. "This drug is nasty stuff, I'll tell you," McCool said. "You've got to be very careful with it. But unless something else comes along, I'm going to be on it for the rest of my life." If pharmaceutical company AstraZeneca gets its way, something else will soon come along for the 3 million Americans who take warfarin to prevent blood clots that can kill. AstraZeneca, which has its U.S. headquarters in Fairfax, has developed what the company describes as a superior alternative to warfarin. Executives say the new drug, called Exanta, works just as well as warfarin in preventing blood clots. But unlike warfarin, Exanta doesn't require regular testing to ensure a patient is getting the right dose. "It's the first oral treatment in half a century for the prevention of deadly and disabling strokes," said Adele Gulfo, a top AstraZeneca executive in the company's Fairfax office. For AstraZeneca, Exanta represents a linchpin in the company's strategy for increasing sales and profits through the rest of the decade. The company, which has about 4,800 employees in Delaware, is counting on Exanta and a handful of other newer prescription drugs to make up for flagging sales of older products. Company executives won't disclose revenue projections for Exanta, but some analysts estimate sales of the drug could reach $3 billion. "Exanta is the next big thing for these guys," said Susan Cross, a pharmaceutical analyst with Wilmington Trust. Finding balance Prescribing warfarin is a balancing act for doctors because its effects are unpredictable, making regular blood testing necessary. Some patients need to vary doses daily to make sure they're getting just the right amount. Too much warfarin and the patient is at risk for bleeding, too little and the patient is at risk of having a stroke caused a blood clot. Safety problems notwithstanding, warfarin also saves lives preventing strokes - a fact that's undisputed even AstraZeneca. Commonly referred to as a blood thinner, warfarin works inhibiting coagulation, the medical term for blood clotting. Clinical trial results showed warfarin could cut the risk of stroke up to 86 percent among patients with irregular heartbeat, a condition that makes a person susceptible to stroke. But the prescribing information for warfarin also warns of the risk of a "fatal" hemorrhage and urges doctors to monitor patients on the drug closely. A spokeswoman for Bristol-Myers Squibb, which markets Coumadin, declined to comment for this article. In contrast with its older rival, Exanta won't require dose adjustments. And the new pill doesn't have warfarin's tendency to interact badly with other medications and certain types of food, said Gulfo, who is responsible for overseeing sales and development of AstraZeneca's cardiovascular medicines in the United States. Although it has advantages over warfarin, Exanta has shortcomings as well, including bleeding risk. Clinical testing results also raised questions about the possibility that Exanta damages the liver. And before American patients can start taking the drug, AstraZeneca will need to persuade regulators at the U.S. Food and Drug Administration that the potential risk for liver damage is more than offset Exanta's benefits. AstraZeneca, which has its world headquarters in London, hopes to begin selling Exanta in the United States early next year. The prescription drug already is available in Germany, and the company expects to introduce Exanta in other European countries later this year. FDA to rule As a matter of policy, FDA officials won't comment publicly on upcoming decisions. But AstraZeneca will soon get a clear indication of Exanta's chances for approval. A panel of medical experts is scheduled to meet Sept. 10 to review AstraZeneca's application and make a recommendation on whether the FDA should approve Exanta. The federal agency isn't obligated to follow the recommendation of an advisory panel, but it typically does. Exanta's effect on the liver is sure to be a focus of discussion at the advisory panel meeting. In clinical testing conducted AstraZeneca, about 6 percent of patients experienced an elevation in enzymes produced the liver. Such an elevation can sometimes be a warning sign that a patient is headed for liver failure. In the case of Exanta, however, the elevation seems to be temporary and doesn't appear to lead to lasting liver damage, said Sir Tom McKillop, chief executive of AstraZeneca. Still, McKillop said the potential for serious liver damage couldn't be ruled out, and he said patients receiving Exanta will need to be watched for signs of problems. "The demand in the marketplace from patients and physicians for Exanta will be very considerable, but we need to be very disciplined in how we launch this product, so that nobody runs an undue risk," McKillop said in a telephone interview. If the FDA approves Exanta, AstraZeneca expects that the agency will require blood testing to monitor patients for elevated liver enzymes. AstraZeneca executives also acknowledged that the FDA may insist Exanta carry a so-called black-box warning - the strongest type of warning - to alert doctors to the potential risk of liver problems. Some Wall Street analysts have speculated that the FDA may initially limit Exanta to short-term use in patients undergoing orthopedic surgery, which has a high potential for causing blood clots. But AstraZeneca sees a greater market opportunity in the drug's long-term use, especially in patients with irregular heartbeat, which increases the risk of stroke fivefold. About 2.2 million U.S. patients have irregular heartbeat, known medically as atrial fibrillation. A new drug, especially one with questions about its safety, can have trouble competing against established rival drugs. But Exanta likely won't have as much trouble winning converts because it will go up against a rival known for its safety risk and inconvenient dosing, analysts said. In the words of Merrill Lynch pharmaceutical analyst James Culverwell, the alternative to Exanta is "rat poison." Rat poison saves lives Warfarin, which grew out of research in the 1930s scientists at the University of Wisconsin, was indeed first used commercially as a rat poison. And warfarin, which causes rats to bleed to death, remains the most widely used rat poison in the world, according to the Wisconsin Alumni Research Foundation. But scientists also determined that warfarin's anti-clotting properties could ward off strokes. And in 1954, the drug was introduced in the United States under the brand name Coumadin. The drug was originally marketed Endo Laboratories, which was acquired in 1969 Wilmington-based DuPont Co. DuPont sold Coumadin up until 2001 when it sold its pharmaceutical business to New York-based Bristol-Myers Squibb. Warfarin was the seventh most prescribed cardiovascular medication in the United States last year. Despite its safety risks, warfarin remains widely prescribed because, doctors say, nothing can match its effectiveness at preventing the blood clots that cause strokes. Strokes, which occur when a clot blocks the flow of blood to the brain, are the third leading cause of death in the United States and the leading cause of disability in adults, according to the American Heart Association. The likelihood of stroke increases with age. "Using warfarin is a double-edged sword, but it has been shown clearly to reduce the chances of a stroke," said Edward Goldenberg, one of McCool's doctors and a cardiologist with Cardiology Consultants, which has offices throughout Delaware. Even after he suffered the internal bleeding in late July, McCool said he never considered dropping warfarin because he didn't want to run the risk of a stroke. Immediately after he suffered the bleeding episode, McCool's doctors ordered daily testing to ensure he was getting the right dose of warfarin. Doctors only recently scaled the testing back to once a week for McCool, who runs an insurance agency with his son in Elkton. On top of the testing, McCool has to watch his diet closely. Lettuce and other leafy green vegetables can play havoc with warfarin's effectiveness because they contain vitamin K, which promotes blood clotting. Warfarin works blocking the liver's use of vitamin K. 20 years to develop AstraZeneca's quest to develop an alternative to warfarin began 20 years ago at a company lab in Molndal, Sweden. After years of trial and error, company scientists developed an experimental compound that appeared to achieve the same level of anti-clotting as warfarin but without the inconvenient testing and dietary restrictions. The compound, later called Exanta, works interfering with thrombin, an enzyme that plays a key role in blood coagulation. AstraZeneca launched a series of clinical tests to evaluate the safety and effectiveness of Exanta. The drug was tested in 17,000 patients in 30 countries. Dr. Jonathan Halperin, a professor at the Mount Sinai School of Medicine in New York, said two major company-sponsored trials he supervised demonstrated that Exanta was as good as warfarin in preventing blood clotting. Exanta also carried less risk of bleeding and a lower potential for food and drug interactions, Halperin said. He added, though, that questions persist about the effect on the liver. Gulfo, the AstraZeneca executive, conceded that patients on Exanta will need to undergo blood testing to monitor the functioning of their livers, but their dosage won't have to be constantly adjusted.The small percentage of patients who experience signs of liver trouble can stop taking Exanta and go back on warfarin, she said. McCool is eagerly awaiting the FDA's decision. He said he would welcome any drug that could free him from warfarin. "If this new drug gets approved and becomes available, you can believe I'll be talking to my doctor, and I won't wait," McCool said. "If it does turn out to really be better, I'd want to jump on it right away. I know better than most the dangers and problems with Coumadin." Contact Ted Griffith at 324-2880 or [email protected].
END of News Article
.............................
Response to friend from 'AL Capshaw':
Thanks for the interesting article Don.
As usual, the alarmist media over exagerates the risks and problems with Coumadin / Warfarin (yes, it is 'rat poison'). Unfortunately, its effects are highly dependent on Vitamin K levels and drug interactions so care must be taken when changes in medication or diet occur. Consistency in diet and medication is the key to successful regulation.
On the other hand, with PROPER monitoring and understanding of 'reasonable' variation limits, it can be managed by most people. DAILY testing tells me that the Doctor in the article doesn't know how to properly manage Coumadin. It takes 3 to 4 days for a change in dose to 'settle out' so daily tests and dosing changes GUARANTEE that the patient's INR (a measure of clotting time) will go on a roller coaster ride. A GOOD Coumadin Clinic would know how to manage their patients much better than the doctor in the article! Testing (and dose changes) should NEVER be done more often than every 3 or 4 days in the worst cases. For most patients who are experiencing 'symptoms' testing once a week is usually the preferred course, then every two weeks, and finally every 4 to 6 weeks as the patient's INR stabilizes. Home testing is the latest craze. It is common in Germany and slowing gaining acceptance in the U.S. There are 3 or 4 companies that manufacture testing instruments that are approved for home use.
The most likely scenario for Exanta will be limited approval for surgeries as indicated in the article, then the lucrative 'Atrial Fibrilation' market, and finally for Valve Replacement patients.
I noticed the author never got around to COST. You can bet the cost of a NEW Patented anti-coagulation drug is going to be VERY HIGH and probably not covered by many (most?) insurance policies. My drug coverage policy will only pay for GENERIC (Warfarin). If I want to go with the Brand Name Coumadin, I have to pay the difference which is not insignificant. Fortunately, my mail order drug company uses an Israeli made generic warfarin that is well respected and can easily be split by hand (not the case for Coumadin). I experienced NO changes in INR following the switch over.
EXANTA is a welcome addition to the anti-coagulation scene, but I expect it will be MANY more years before it becomes the defacto standard or affordable by most patients.
Al Lodwick, R.Ph. and Coumadin Clinic Director in Colorado has a very informative website at www.warfarinfo.com which addresses just about everything anyone would ever want / need to know about warfarin / Coumadin, including Exanta and it's approval status.
'AL Capshaw' (Coumadin / warfarin user for over 2 years with stable INR)
Life is good 
