FDA Panel Rejects AstraZeneca Drug

[GravyRPH]

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BETHESDA, Md. (Reuters) - A U.S. panel of medical experts recommended on Friday that U.S. regulators reject AstraZeneca's (AZN.L: Quote, Profile, Research) (AZN.N: Quote, Profile, Research) application to sell its anti-clotting drug Exanta.

Panel members voiced doubts about the drug's safety and effectiveness. They voted against all three proposed uses, including long-term therapy to prevent strokes in patients with the heart disorder atrial fibrillation.

The committee also said the drug's risks outweighed any benefits for long-term use to prevent blood clots in the veins, as well as for a short-term therapy to prevent clotting in patients undergoing knee replacement surgery.

"My risk concerns are lower for short-term use, but they don't go away," said Steven Nissen, a panelist and cardiologist at the Cleveland Clinic in Cleveland, Ohio.

Exanta has been associated with raised liver enzymes, a possible sign of damage to the organ, in some patients. Panel members also overwhelmingly rejected the company's plan to manage possible liver toxicity.

Most panel members said they had a "high" level of concern over the drug's risk of liver toxicity when used over the long term, and said the company's proposal to manage the risk to patients was not adequate.

Susanna Cunningham, a nursing professor at the University of Washington in Seattle and non-voting panel member, said "I don't think the public is willing to accept liver failure. Livers are hard to come by."

The experts encouraged the FDA to require additional safety trials to see whether patients treated short term developed liver damage after stopping therapy, and to determine the possible risk of heart failure.

"It doesn't look promising in terms of the cardiovascular risk," Nissen said.

A number of other health experts pressed panelists on the need for a more manageable anti-clotting agent than warfarin, the only other anticoagulant pill on the market.

 

[MRBPharmD]

BETHESDA, Md. (Reuters) - A U.S. panel of medical experts recommended on Friday that U.S. regulators reject AstraZeneca's (AZN.L: Quote, Profile, Research) (AZN.N: Quote, Profile, Research) application to sell its anti-clotting drug Exanta.

Panel members voiced doubts about the drug's safety and effectiveness. They voted against all three proposed uses, including long-term therapy to prevent strokes in patients with the heart disorder atrial fibrillation.

The committee also said the drug's risks outweighed any benefits for long-term use to prevent blood clots in the veins, as well as for a short-term therapy to prevent clotting in patients undergoing knee replacement surgery.

"My risk concerns are lower for short-term use, but they don't go away," said Steven Nissen, a panelist and cardiologist at the Cleveland Clinic in Cleveland, Ohio.

Exanta has been associated with raised liver enzymes, a possible sign of damage to the organ, in some patients. Panel members also overwhelmingly rejected the company's plan to manage possible liver toxicity.

Most panel members said they had a "high" level of concern over the drug's risk of liver toxicity when used over the long term, and said the company's proposal to manage the risk to patients was not adequate.

Susanna Cunningham, a nursing professor at the University of Washington in Seattle and non-voting panel member, said "I don't think the public is willing to accept liver failure. Livers are hard to come by."

The experts encouraged the FDA to require additional safety trials to see whether patients treated short term developed liver damage after stopping therapy, and to determine the possible risk of heart failure.

"It doesn't look promising in terms of the cardiovascular risk," Nissen said.

A number of other health experts pressed panelists on the need for a more manageable anti-clotting agent than warfarin, the only other anticoagulant pill on the market.

...for my stock in AZN that is!

 

[GravyRPH]

Indeed. 😉

 

[Glycerin]

A number of other health experts pressed panelists on the need for a more manageable anti-clotting agent than warfarin, the only other anticoagulant pill on the market.

Are antiplatelets the same as anticoagulants? I'm asking because I know that clopidogrel is an antiplatelet which prevents blood clots, yet this article talks about a need for a more manageable anti-clotting agent. Is it that warfarin and clopidogrel aren't similar?

Just wonderin'. 🙂

 

[GravyRPH]

"Plavix, similar to aspirin, is effective in treating arterial clots (stroke, heart attack, peripheral arterial disease), whereas coumadin is effective in treating venous clots (deep vein thrombosis or pulmonary embolism).

Arteries are thick blood vessels with fast flowing blood.Blood clots in arteries are typically triggered by underlying roughening of the artery wall (= arteriosclerosis; atherosclerosis); blood platelets get stuck to the roughened blood vessel wall and form a clot. Thus, the medication of choice in trying to prevent thrombosis in arteries (i.e. stroke, heart attack, peripheral arterial disease, retinal artery thrombosis, etc.), are medications that act against platelets.

Veins are made up very differently compared to arteries. Veins are thin blood vessels with slow flowing blood. Blood clots that form in veins (deep vein thrombosis, pulmonary embolism) are mainly made up of clotting proteins; platelets do not play a big role in venous clots. Coumadin (= warfarin) is an effective "blood thinner" by preventing the production of clotting factors in the liver, increasing the INR. It is therefore the drug of choice in venous thrombosis. Anti-platelet drugs do not play much of a role in preventing venous clots.

Occasionally, clots in arteries originate from one of the two left heart chambers (= left atrium, left ventricle) and travel from there with the blood stream to the brain, the retina, or the extremities. This typically happens in atrial fibrillation (= irregular heart beat). Such a clot is called an arterial embolism (= arterial thromboembolism; plural: "emboli"). These arterial emboli resemble the type of clots seen in veins, i.e. they have little platelet participation. They are therefore best treated with coumadin, not with anti-platelet drugs, even though they are clots in arteries"

 

[MALA]

Just a couple of questions:
Can coumadin cure or prevent vericose veins?
Arterial embolism? Is that considered the "silent killer" that is hard to detect with tests and x-rays?
Also, Plavix - coumadin, would you say that high cholesterol is complementary (for lack of a better word) to these ailments that require those meds? And then there's the roller coaster of high blood pressure. Do you find that if you have high cholesterol, you would normally have high blood pressure, and then you need blood thinners, etc? Would any of these medications clash against each other in certain individuals?

 

[GravyRPH]

"Serum warfarin concentrations were unchanged in warfarin-stable patients during and following an 8-day course of clopidogrel (75 mg/day). Patient INRs were likewise unchanged. No increase in side effects (including bleeding) was noted. "

I don't think coumadin would help vericose veins, but I doubt you would use such a high risk medication to treat it.

Cholesterol, blood pressure, and all these problems are completely intertwined.

 

[MALA]

Gravy, I understand that over the years, all these different medications will cause your liver to take a beating. In your opinion, or if you're pretty sure, how many years of daily intake of these meds before you're being treated for dialysis?
It sounds funny that I want to be a pharmacist, but I myself don't believe in taking medication for every little ailment (and knock on wood, it just happens that I'm healthy at the moment). But doesn't it drive you crazy that you see people taking asthma medication, cholesterol meds, heart meds...and they smoke, eat unhealthy foods everyday?....I don't want to mind what others do, but I wonder how long those meds can sustain a person while they "live on the edge"?

 

[GravyRPH]

Gravy, I understand that over the years, all these different medications will cause your liver to take a beating. In your opinion, or if you're pretty sure, how many years of daily intake of these meds before you're being treated for dialysis?

6.2 years. :/ I don't think anyone could predict any sort of time frame, if at all.

It sounds funny that I want to be a pharmacist, but I myself don't believe in taking medication for every little ailment (and knock on wood, it just happens that I'm healthy at the moment). But doesn't it drive you crazy that you see people taking asthma medication, cholesterol meds, heart meds...and they smoke, eat unhealthy foods everyday?....I don't want to mind what others do, but I wonder how long those meds can sustain a person while they "live on the edge"?

I know a nurse who swears that medications are poisons, and that some may do more good than harm but they all do some sort of harm. That's your prerogrative to believe. I am not here to judge what others are doing. I am here to try to improve your health. I partly do smoking cessation counseling and in that capacity I try to get them to quit. If I'm ever in a position otherwise to provide that counseling I will, but I don't try to get worked up about it. It can be frustrating at times; 1 step forward, 2 steps backward....hopefully I can get them going 2 steps forward, and only 1 step backward.

 

[MALA]

That's really terrific Gravy. I'll pick your brain one more time and leave you alone- I promise. Now, as you see I'm a pre-pre-pharm, (still taking gen chem) with all the knowledge a pharmacist posesses, being able to read and understand all ingredients and interactions that a drug contains. Was it a shock for you to read how that anti-depressant med (the name has escaped me) lead to suicides? You (meaning all pharmacists in general) see the new drugs that come out, know the ingredients and interactions, did it occur to anyone that a certain ingredient in this drug could trigger something as this? Is this one of those "why did the hurricane move west instead of north" type of questions? I apologize if these questions seem very elementary. It amazes me how much a pharmacist knows and I would trust a pharmacist before a Dr when it comes to medication advice.

 

[GravyRPH]

I haven't seen the actual study data to back up the FDA's claim. I am still skeptical that anti-depressants increase the rate of suicide in and of themselves without regard to the obvious underlying condition. To me it's like saying red v8's go faster because they're red.

 

[bananaface]

We would need to see the study to see if there is any cause for alarm. Just for general information, when a patient begins treatment with an antidepressant, there is an adjustment period. The side effects usually appear at first, and wane over a period of weeks. Improvement in symptoms of depression takes gradually place over a few weeks. For a patient who already has suicidal feelings, this transition can, although rarely, yield a sense of empowerment before it yields relief from despair. So, patients who have had suicidal thoughts should begin antidepressant use very cautiously (ie: with monitoring). Once the transition period ends, these patients are usually much better off than before therapy.

MALA- You may feel better about medication use if you use this line of reasoning: there are cases in which the risks or known consequences of NOT taking a medication are greater then those associated with taking it. For every drug we evaluate the use of, we hope that the benefits outweight any potential side effects. Keep in mind that pharmacists not only recommend drugs, but may also recommend that a drug be discontinued or another medication substituted. In either case, we are working to accomplish whatever is in the best interest of the patient.

 

[MALA]

I see. I appreciate your viewpoints, it really does help me to see clearer about these topics. Thanks so much Gravy & Banana!

 

[MNnaloxone]

I actually presented Exanta to pharmacy departments as part of my residency interviews. I'm actually kinda shocked that the FDA shot it down.

The clinical data was great (SPORTIF III & V) showed equal efficacy to coumadin. Can't pull it off the top of my head, but fewer bleeds in the Exanta group. Sure, there were LFT elevations, but from my take, they were less that statin occurances. They were infrequent, transient, and returned to WNL after drug d/c. Heck, it was approved almost a year ago in France (DVTs???). Not that I like France... 🙄

Methinks A-Z pissed someone off at the FDA. Otherwise, a lot of us were completely wrong in our study analysis.

 

[GravyRPH]

Ya, I knew someone on here mentioned they were doing a presentation on it awhile back and that's why I thought this post would be of interest. I was shocked as well. I was under the impression the LFT increases were transient and reversible. I don't think this will be the end of the Exanta story.

 

[bananaface]

I don't think this will be the end of the Exanta story.

Perhaps they are being required to rename it so it isn't a sound alike to Mylanta?

 

[MNnaloxone]

'Exanta' is fine. Try saying ximelagatran a couple dozen times in a presentation... 😱

Just think, if warfarin goes away, that's one more drug that we can't amaze new pharm students with the story of its naming. We'll be left with Lasix and Vanco.