Dear Dr. Dave...

With the recent wishy~washy black box warning that the FDA just slapped on Avandia®, I was hoping to tap into your thoughts as a practicing primary care physician on how this might affect your prescribing patterns. This is now the third (and most serious) black box warning for this once magnificent drug. The FDA voted 8 - 7 in keeping it on the market as opposed to pulling it all together by a very slim margin.

Now that there is so much heat on Avandia®, GSK looks like they are trying to "spin it" by stating that the other TZD on the market, Actos®, is no safer and that they will immediately start a head-to-head study comparing the two drugs straight up. Just so we are all clear, the new black box warning for Avandia® states: "this drug may cause a heart attack". I think GSK might be playing dirty pool by obviously going with the old "If I go, You are going with Me" type attitude. Do you think GSK is really trying to say that there is a Class Effect amongst the TZDs (something they never would have thought of publicly suggesting before, when they had the county fair's prize pig year after year)?

And to be fair in this whole ugly mess, Takeda's Actos® also has two black box warnings dealing with dangerous side effects.



The two type II diabetic drugs combined pulled in a record setting 6 Billion Dollars in the USA alone in 1996. That is about the same number of dollars that Vioxx® and Celebrex® were registering in 2003 and 2004 (Vioxx® was voluntarily withdrawn from the market on September 28, 2004).

This is almost exactly what Merck was doing in covering-up the early Vioxx® precautions and warnings:
(for the full Wall Street Journal article)
http://online.wsj.com/article/SB119524107384696003.html?mod=yahoo_hs&ru=yahoo

"Over a period of several years, drug maker GSK was so concerned about a prominent physician's negative views of its diabetes drug that it engaged in a concerted effort to intimidate him and stifle his opinion, a report by the U.S. Senate Finance Committee found."






This looks like it could bring about a dangerous "hand slapping" from the FDA and provide enough anger for them to look closely at Actos® safety data!
(for the full AP Washington DC article)
http://biz.yahoo.com/ap/071115/takeda_diabetes_ads.html?.v=1

"The ads from Japan's largest drug company, which will run Friday, November 16th in 82 U.S. newspapers, will read:

'Actos® has been shown to lower blood sugar without increasing your risk of having a heart attack or stroke.'

The language walks a careful line between what FDA says is -- and isn't -- known about the comparative safety of diabetes drugs".






Dr. Dave, what I am asking from you personally is the following:

• I am sure that you correspond with former medical school classmates and other local physicians in your (albeit small) community...What feedback are you hearing from them in regards to all of this controversy surrounding the TZDs in 2007?
• Would you mind asking a few of them, before responding?
• Do you now hesitate in writing a prescription for either Avandia® or Actos® for your type II diabetic patients?
• Are any of your patients asking about Avandia® or Actos®, since they both have been in the news so much?

I realize this feedback will be from a small group, but it should be random enough to at least get a pulse of current mindset and prescribing behavior.



[size=+3]Thank you Dr. Dave for being here for us as a resource![/size]

 

"The two type II diabetic drugs combined pulled in a record setting 6 Billion Dollars in the USA alone in 1996." As neither one of these drugs was commercially available until 1999; I wonder, How did they made 6 billion dollars. You must work for CBS where the news is made up to fit the story!! good try bucko!!

 

Hey, thanks for the catch. My bad - I think I had a brain fart by typing 1996 rathen than 2006!

I fixed the date in the attached quote.

Thanks again for making the catch so Dr. Dave can have all the facts first hand, before responding...

 

Dr. Dave,

You have a pretty sharp eye or an excellent memory (or both), because I am the OP of this thread and I was also the OP of that other thread that you pointed to way back in July - Before Avandia® really showed its true colors.

Thanks again for your incite.

I'll wager you a 5 dollar bill that both Actos® and Avandia® get pulled by the FDA before next Summer 2008. How 'bout it?

I think the FDA will indeed group them both as falling into the Class Effect category along with that other TZD: Rezulin®, from days gone by.

 

Rezulin was pulled for liver issues - completely different issue. So no, the would not be lumped in with Rezulin and pulled from a class effect.

 

Uhhh...I don't think you are Dr. Dave responding here.

And you are wrong about the Class Effect of lumping all three drugs together after both Avandia® and Actos® are pulled by the FDA. You were right about the one reason that Rezulin® was pulled, but that did not mean that it also had the capability of causing other end organ problems such as those effecting the heart and kidneys.

Let history show for the record that all of the TZDs will be looked back upon as terrible drugs that ended up with record breaking lawsuits (that will make the Vioxx® debaucle look pale in comparison). When companies hide data, change data and pressure/threaten doctors who are part of investigation teams - they open themselves up to huge fines and penalties.

What the FDA needs to stop doing is levying such huge multimillion dollar settlements and instead place people in prison for such wrong doings. I guarantee the fraudelent activity would come to a screeching hault.

Landmark cases that should have equated to prison time:

Phen-phen®...estimate 8 -10 Billion Dollar Settlement...American Home Products (now Wyeth)
Lupron® False Marketing/Medicaid fraud...875 Million Dollar fine...TAP (Takeda and Abbott Labs Partnership)
Oxycontin® Fraud in denouncing potential of addiction...634.5 Million Dollar fine to the top 3 executives (Purdue Pharma) More to come via Class Action Lawsuits
Vioxx®...4.85 Billion Dollar Class Action Settlement Merck (knowingly hid data) More to come via Class Action Lawsuits




In fact both Avandia® and Actos® are presently being investigated for possible Cancer causation of the Liver...Stay tuned for that little discovery to be announced before year's end.

 

Dr. Dave,

So let me get this straight...There have been 3 TZD Class drugs approved by the FDA since 1997 and 1 of those three (Rezulin®) was promptly pulled in 2000 because of damage to the liver. In the interim, Avandia® and Actos® came on to the type II diabetic scene in a big time way with gigantic revenue for their individual companies. Fast forward to present day (November 23, 2007) and Actos® now has two black box warnings and Avandia® has three. Hmmmmm? Sounds a little too close for comfort to just casually throw out the idea that there probably is a class effect in play here.

Dr. Dave, had Rezulin® not been so quickly withdrawn from the market back in 2000, do you think that it might have also had the cadiac problems that both Actos and Avandia are displaying?

Dr. Dave, As you probably are aware, Cafepharma has advertisements on their website in addition to very helpful "in the news" topics concerning the pharmaceutical world. And just today, there is an article posted on the right hand side of this webpage titled: "Lawmakers Warn Drug Makers To Knock It Off After Avandia® Debacle - Part II"
http://www.lawyersandsettlements.com/articles/01604/avandia-debacles.html

The article is very good and a worthwhile read about the FDA cracking down harder on potentially problematic drugs. But what I found really interesting was this little gem at the bottom of the article itself:

Avandia Legal Help
If you or a family member have used Avandia and have suffered heart attack or liver damage after taking Avandia, please contact a lawyer involved in a possible [Avandia Lawsuit] who will review your case at no cost or obligation.
I certainly do not want to be accused of "making this stuff up", so I ask you to open this attached link and see for yourself...Why would law firm be gathering potential clients in what looks to be a forthcoming lawsuit against GlaxoSmithKline in regards to both cardiac and/or liver damage?
https://www.lawyersandsettlements.com/submit_form.html?label=avandia-heart-attack&ref=article1604

One more question for you before I log off, Dr. Dave. If a particular drug has two black box warnings (forget three), why would you prescribe it ever again?
I know the "canned answer" of the benefits still outweigh the risks, but are there not other choices that a physician can make - Just to be on the safe side, especially with all this controversy and questions hovering around TZDs in general?

 

Dave,

I think some paralegal is going on a fishing expedition.

 

Dr. Dave, OP here and wondering if you are ready to continue on with our little wager?

Have you seen the most recent news involving Actos®, in that it has the exact same dangerous potential as Avandia®...

 

Bloomberg

Takeda's Actos Has Same Heart Risks as Glaxo's Avandia, Researchers Find
By Kanoko Matsuyama - Aug 24, 2010 3:00 PM CT

Takeda Pharmaceutical Co.’s best- selling diabetes drug Actos causes as many heart problems as Avandia, the GlaxoSmithKline Plc pill whose sales fell after it was linked to higher heart-disease rates, a study found.

Avandia generated $3.3 billion in the year before a 2007 study showed a 43 percent higher chance of heart attacks and helped Actos become the market leader. Patients taking either Avandia or Actos increased the risk of heart attacks, heart failure or death by 4 percent, according to the study published today in the American Heart Association journal, Circulation.

U.S. regulators are reviewing whether Avandia, which comes under the same class of treatment as Actos, should be taken off market after a panel advised July 14 that new warnings about heart risks be added to its prescribing information. The latest study, the first to compare the two drugs directly, suggests the risks are tied to that category of medicines, said Jenny Gunton, an endocrinologist at the Garvan Institute of Medical Research.

“It just maybe increases the worry of using either of the drugs,” Gunton, who wasn’t involved in the study, said in a telephone interview from Sydney. A rate of 4 percent is “pretty high” given the short study period, she said.

The study involved more than 36,000 diabetes patients with an average age of 54 years and took place over 33 months, including 14 months of treatment on either medication. Among the patients, 602 who took Avandia and 599 Actos users suffered either a heart attack or heart failure or both, or they died, the study showed. The tally included 217 deaths in each group.

Sedentary Lifestyles

About 23.6 million Americans have diabetes, mostly the Type 2 variety linked to being overweight and sedentary, according to the National Institutes of Health. The disease is characterized by the body’s inability to use insulin to break down blood sugar for energy. The illness increases the risk of heart disease, stroke and kidney damage. Avandia and Actos work by increasing the body’s sensitivity to insulin.

Glaxo fell 27.5 pence, or 2.2 percent, to 1,200 pence as of 4:35 p.m. in London trading. Takeda gained 0.3 percent to 3,915 yen on the Tokyo Stock Exchange.

Avandia generated sales of $1.1 billion last year for Glaxo, the U.K.’s biggest drugmaker. The London-based company said last month it would record a 1.57 billion-pound ($2.4 billion) charge in the second quarter to settle cases including claims that Avandia led to heart attacks, adding to 2.3 billion pounds it previously set aside for legal costs.

The Avandia study in 2007 was an analysis of data from 42 studies involving 15,560 patients who took the drug and 12,283 people who were given other medications or a placebo. Patients on Avandia were 64 percent more likely to die from cardiovascular causes, though those findings could have resulted from chance, researchers in that study said.

Actos had sales of 384.7 billion yen ($4.6 billion) in the year ended March 31. The drug halted progression of heart disease in diabetics, a 2008 study funded by the company showed.

 

This "study" was a retrospective chart review....not exactly science as seen in over 120,000 previous patients on pioglitazone who had no elevated risk in MACE. Check your data...and turn off the TV.

 

Hi DD,

I am the original poster and just checked back in to see if any updates had been made to this thread...

That said, I am curious to know if you have been following the most recent news regarding Takeda's Actos? Particularly the German and French Governments banning Actos due to Actos causing Cancer of the Kidneys.

Remember when I suggested the "cancer" thing about 3 years ago?

Hope you are doing well.

By the way, where's my 5 dollars. LOL

 

OP here...

Just an update for you Dr. Dave.

Takeda laid off 700 folks this past week --- And that # will be far greater by the end of this year as Actos goes generic and the "pending" lawsuits begin their ugly journey.

Hope you are doing well.

ps. As we speak, Takeda is having their annual National Sales Meeting in Las Vegas at the MGM Grand Hotel. They have booked a band called "Maroon 5" as opening night entertainment for the remaining company employees - It cost them 1.5 Million Dollars for the 45 minute show (yes you read that correctly). Any thoughts about that?

 

The booking of the band Maroon 5 turned out to be a rumor perpetuated here, most likely by helped out by the 700 people who were abruptly let go.