Amgen's unethical practices

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Oct 21, 2012
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Maxiton said:
LA and cohorts have been under Federal investigation for at least a couple of years now for possible criminal acts surrounding doping: fraud, bribery, and who knows what else. Likewise, several doping doctors, tons of riders, etc, have been under multiple investigations in their own countries, in some of which doping with PEDs is itself a crime, to saying nothing of PED trafficking.
I thought the Federal case had been dropped at the begining of the year and this was what led to the USADA case or was there another FED case?
 
May 14, 2010
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blutto said:
...and if you want a real good belly laugh take a peek at Weisel's perfomances at the Masters World Championships in the late 80's and early 90's...

...miracles or what?...

Cheers

blutto
Cheers, blutto. I wasn't aware of that. Guess he figured if it was good enough for his prodigy, it was good enough for him.

Tom375 said:
I thought the Federal case had been dropped at the begining of the year and this was what led to the USADA case or was there another FED case?
The fact it's been dropped (for now) doesn't change that it went on for a couple of years.
 
Aug 27, 2012
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Merckx index said:
Not to depress anyone here further, but many of the illegal or unethical practices reported for Amgen have been pretty much standard fare for drug companies for decades. For example, new graduates of medical schools have long been given gifts by drug companies, and encouraged to work closely with them for special deals.

I won't even get into all the biassed studies by drug companies that are designed to win approval of substances. Big tobacco, of course, has long been a prime example, but the same crap goes on with companies trying to develop medically useful drugs. There are many other issues that are a product of our capitalist system, e.g., companies will not develop a drug unless it has a large profit margin, which means individuals with relatively rare disorders that might be curable often are ignored.
As one who's been on the inside of one of the largest global drug firms for the best part of 20 years, and an additional 10 in other drug and medical technology multinationals, I can agree with most of what is stated in your post and the thread.

However, the debate inside drug firms over ethics is as fierce as it is outside them. In fact often it is even fiercer. There are many people inside these firms with a very high degree of morality; the regulatory framework on promotions, incl. out of label use, and the associated financial penalties are now so high, that most firms have become very very careful. The internal control procedures - in the larger firms - are such that if one gets caught it's often (blamed on) "an overzealous individual" going against the standard company procedure...

And whilst the practices you mention go on, they are by far the minority of what goes on. The majority of promotional activity is geared around "educating" (yes, I know definition...?!) doctors, truly, may be hard to believe for outsiders, but remember doctors do not receive much if any ongoing training about drugs once they leave medical school. And few doctors are able/willing to keep up with advances in drug treatment (which makes up a significant part of daily medical practice) in ways independent of drug companies (eg keeping up with relevant literature). So there is a convenient symbiosis between drug firms and the medical profession.

Likewise on the research side. Many medical specialists depend on drug firms to do research and further their academic careers... Biased studies were very popular 20-30 years ago, much less so now. Too easy to pick the methodology holes (Ed Coyle ring a bell?), much more scrutiny, and regulatory and reimbursement agencies harder to fool. They are however still very popular in the direct to consumer field where the consumer is still more ignorant and easier to fool... (eg. refer discussion in Skins armwarmer thread). But this is much more common in nutraceuticals, supplements, etc than regulated prescription drugs.

The rare disorder field has actually become the new lifeblood of the industry, as one can charge higher prices, particularly for serious disease, as the large "blockbuster" drugs have and are going off patent. To resolve the issue of affordability the industry has developed some innovative pricing solutions, eg means testing and insurance programs, etc.

Off label psychiatry is a complex field. The DSM diagnostic criteria that guide in/off label use are not as "hard and fast", the patient often needs more "drug experimentation" to maximize treatment benefit/side effects, and there is often strong patient/family demand to resolve the symptoms with a pill, rather than perhaps other means. Ritalin has been a favorite beating horse by the popular media for decades. It's a stimulant just like others that have been used in cycling for the best part of a century. Aspirin would not be approvable for general use today as a new drug as the toxicity/side effect profile is so poor, but because it has been around for so long it is accepted with the disclaimers it has.

Often the general drug company debate boils down to your opinion on how much profit drug companies ought to make on health, and how to regulate this via a sensible price mechanism. This is a highly complex debate, and has lead to the existing patent laws on pharmaceuticals, and reimbursement systems that are different for different countries. The promotional control system (ie product claims, advertising, doctor dinners, out of label promotions, etc) is now also highly controlled, in fact much more so than most (if not all) other products one can buy. Taking a doctor lunch or dinner to show a video on a new product has to be declared to the regulator. Tell me any other industry that is that regulated.

Regarding Amgen, it is highly likely that in the mid-late 80's the relationship with USPostal included clandestine drug supply, IMHO. The relationship with Amgen and cycling subsequently would have developed as a function of Thom Wiesel's personal interest in cycling. To what extent that relationship today still involves an "active EPO" component is hard to say but I would guess this to be highly unlikely. Amgen cannot afford it anymore (in terms of reputation risk), nor do they need it anymore (financially).

But yes, an inside mole at Amgen would be great. Meanwhile Blood Medicine by Kathleen Sharp would be a great start. I will certainly have a read.

I also read Weisel's personal sports performances. What he does have going for him is a top level junior ability which presumably would have been drug free. In his book he refers to a seminal training camp he attended in 1985 with Eddy B as a personal milestone. Let me dig out the link, I was going to post this yesterday but decided against it.
 
Aug 27, 2012
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From Eddy B's wiki page, already updated after the LA TdF strips!

"Eddie Borysewicz resigned as coach of the American national team in 1987[10] partly because of disagreements with members of his squad.[11] He started his own amateur team in 1988. Sponsorship by Sunkyong, a Korean electronics firm, ended after a year and Borysewicz sought a replacement in Montgomery Securities. Its chief executive, Thomas Weisel, agreed to a team of 15 that included Lance Armstrong. That team, after several sponsorship changes, became the US Postal Service and Discovery Channel teams for which Armstrong won the Tour de France seven times before those victories were vacated in 2012 after the USADA ruled that Armstrong doped during each of those victories.[12]"
 
Jul 19, 2010
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When you have EPO maker like Amgen sponsoring the biggest cycling event in the US, it's no wonder USAC was worried about the credibility of American cycling.

I think this Amgen scandal is going to be huge like the Enron scandal.
 

mastersracer

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Jun 8, 2010
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Maxiton said:
LA and cohorts have been under Federal investigation for at least a couple of years now for possible criminal acts surrounding doping: fraud, bribery, and who knows what else. Likewise, several doping doctors, tons of riders, etc, have been under multiple investigations in their own countries, in some of which doping with PEDs is itself a crime, to saying nothing of PED trafficking.

What is implied by this Amgen/Weisel/Armstrong/pro cycling/EPO connection, as well as sport-as-vertical-market for Amgen, is, first, that LA is nothing more than marionette and Amgen the manipulator. If there is even a kernel of truth to that, all LA's actions, and those of his co-conspirators, implicate Amgen. In any case, it may be that Amgen and/or their competitors are involved in all this up to their necks; and they may turn out to be the prime movers behind much of it. Again, we are talking about criminal acts here, many of them.

Those are the implications, or some of them.
I am asking what specific criminal activities and/or charges would be implicated? You have simply stated that Amgen may have been involved in illegal activities involving Armstrong. The fact that Wiesel invested in Amgen isn't illegal, the fact that Armstrong took a drug manufactured by them doesn't implicate Amgen in any illegal activity. What would Amgen have to gain by contributing in material ways to PED usage when athletes and unscrupulous doctors create that market all by themselves? FWIW, Amgen's practices aren't untypical of big pharma and they are small players (look at the settlements against the big players).
 
Aug 27, 2012
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mastersracer said:
I am asking what specific criminal activities and/or charges would be implicated? You have simply stated that Amgen may have been involved in illegal activities involving Armstrong. The fact that Wiesel invested in Amgen isn't illegal, the fact that Armstrong took a drug manufactured by them doesn't implicate Amgen in any illegal activity. What would Amgen have to gain by contributing in material ways to PED usage when athletes and unscrupulous doctors create that market all by themselves? FWIW, Amgen's practices aren't untypical of big pharma and they are small players (look at the settlements against the big players).
Agreed. Unless there is testimony under oath of direct unlawful supply (off label and without presciption) from Amgen there is nothing unlawful to anything they have done that I can see.
 
May 14, 2010
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mastersracer said:
I am asking what specific criminal activities and/or charges would be implicated? You have simply stated that Amgen may have been involved in illegal activities involving Armstrong. The fact that Wiesel invested in Amgen isn't illegal, the fact that Armstrong took a drug manufactured by them doesn't implicate Amgen in any illegal activity. What would Amgen have to gain by contributing in material ways to PED usage when athletes and unscrupulous doctors create that market all by themselves? FWIW, Amgen's practices aren't untypical of big pharma and they are small players (look at the settlements against the big players).
It could be that Amgen is merely the innocent manufacturer. In which case it certainly isn't their fault that their honest drug has been misappropriated for misuse and abuse by athletes. The fact that the principle investor and instigator/mentor behind Armstrong & team is also a principle investor in the manufacturer of EPO, Amgen, could simply be a curious coincidence. The fact that a so called black market in EPO developed among Euro athletes just as trials started for the drug in Europe could also be a coincidence. The fact that this black market developed at a time when Amgen was under pressure to find markets for the drug and move as much of it as possible - that, too, could be a coincidence. The fact that the drug found its way to Weisel's team - yet another coincidence. So many coincidences! Remember the "magic bullet" theory of the JFK assassination? This drug is like that. EPO and its spectacular coincidences are the magic bullet of the peloton, and Amgen/Weisel are innocent bystanders. OR . . .

Amgen and a principle investor, Weisel, identified competitive sport as a potentially huge avenue for profit, especially once they had taken a most unlikely canditate for sporting success - former cancer patient Armstrong - and used their drug to transform him into sporting superman. How far would they go to make this happen and maintain it? For the answers, you'll have to ask them. Or maybe we can just wait and let the investigators ask . . . .
 
Jun 19, 2009
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Tinman said:
As one who's been on the inside of one of the ....


Regarding Amgen, it is highly likely that in the mid-late 80's the relationship with USPostal included clandestine drug supply, IMHO. The relationship with Amgen and cycling subsequently would have developed as a function of Thom Wiesel's personal interest in cycling. To what extent that relationship today still involves an "active EPO" component is hard to say but I would guess this to be highly unlikely. Amgen cannot afford it anymore (in terms of reputation risk), nor do they need it anymore (financially).

But yes, an inside mole at Amgen would be great. Meanwhile Blood Medicine by Kathleen Sharp would be a great start. I will certainly have a read.

I also read Weisel's personal sports performances. What he does have going for him is a top level junior ability which presumably would have been drug free. In his book he refers to a seminal training camp he attended in 1985 with Eddy B as a personal milestone. Let me dig out the link, I was going to post this yesterday but decided against it.
The description of the Arensep promotional program openned up an entire source for diversion of excess EPO via the 19% bonus plan. Amgen's representatives couldn't be risk-taking by direct distribution. Just having a program where there is excess epo than the audited amount invites illegal distribution. Wiesel, Postal and any other team would just need a name at a facility with a willing seller/donor to create a reliable source of distribution. That would be a crime as far up the food chain as it could be chased.

As for Eddie B's contribution towards milestones with Wiesel's help, my opinion's been the same.

This is as important as selecting alternatives to the UCI.
 
That would make a ton of sense if Armstrong was the first and only person to ever win anything using EPO, but thats far from the case. According to Tyler Hamiltons book, the team didnt even have an organized doping program until '96 i believe. If Weisel seriously planned the whole thing around doping his team then why were they not all on EPO right from the start?
 
Sep 29, 2012
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Oldman said:
Wiesel, Postal and any other team would just need a name at a facility with a willing seller/donor to create a reliable source of distribution. That would be a crime as far up the food chain as it could be chased.
This just triggered my spider senses and sent them into tingling overdrive.

Can you expand on this please? It may seem bog obvious to you, but I would like your take on it - likelihood / impact / feasability, etc?
 
May 14, 2010
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zlev11 said:
That would make a ton of sense if Armstrong was the first and only person to ever win anything using EPO, but thats far from the case. According to Tyler Hamiltons book, the team didnt even have an organized doping program until '96 i believe. If Weisel seriously planned the whole thing around doping his team then why were they not all on EPO right from the start?
It isn't necessary for the whole thing to have been planned in advance, in order for it to have happened. In fact, that isn't even possible, since they couldn't have known a Lance Armstrong would come along. No doubt the whole flow of the drug into sport started somewhat informally and was haphazard. Prior to Armstrong, much of the peloton had been using EPO for years. But once the former cancer patient did come along, the potential for maximizing awareness of the drug and its potential in sport would have been obvious. And as long as Armstrong enjoyed success, a lot of people stood to make a lot of money off of it. Just think of what people in the know were making on insurance bonuses and sports betting alone. We're talking millions! These include people inside the UCI, and anyone else willing to wager big money on a sure thing. And then we get to the sponsors and the race organizers. And all the while, the drug flowed . . . .
 
Sep 29, 2012
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Maxiton said:
And as long as Armstrong enjoyed success, a lot of people stood to make a lot of money off of it. Just think of what people in the know were making on insurance bonuses and sports betting alone. We're talking millions! These include people inside the UCI, and anyone else willing to wager big money on a sure thing. And then we get to the sponsors and the race organizers. And all the while, the drug flowed . . . .
This is something that I reckon is missing from the story, given CSE or Tailwind put > $400k bet down on Armstrong not winning one, but 6 in a row. In a row. Not 6 total, but in a row.

It seems crazy to me to think that
1. he did it just with EPO and no UCI / race owner complicity
2. noone else made a similar bet, given 1
 
Aug 27, 2012
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Maxiton said:
It isn't necessary for the whole thing to have been planned in advance, in order for it to have happened. In fact, that isn't even possible, since they couldn't have known a Lance Armstrong would come along. No doubt the whole flow of the drug into sport started somewhat informally and was haphazard. Prior to Armstrong, much of the peloton had been using EPO for years. But once the former cancer patient did come along, the potential for maximizing awareness of the drug and its potential in sport would have been obvious. And as long as Armstrong enjoyed success, a lot of people stood to make a lot of money off of it. Just think of what people in the know were making on insurance bonuses and sports betting alone. We're talking millions! These include people inside the UCI, and anyone else willing to wager big money on a sure thing. And then we get to the sponsors and the race organizers. And all the while, the drug flowed . . . .
The Eddy B program was up and running when Armstrong joined it early 90's. Eddy claims LA as "his" discovery, not Carmichael's. And Eddy approached Thom Weisel re funding a cycling team.
 
May 14, 2010
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Tinman said:
The Eddy B program was up and running when Armstrong joined it early 90's. Eddy claims LA as "his" discovery, not Carmichael's. And Eddy approached Thom Weisel re funding a cycling team.
So?


@¶ÓÕ俖俦値
 
Jul 25, 2009
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This info adds some more context to Dim's diagram which connected the Weasel and Amgen. Amgen doesn't seem to have followed all the rules (surprise).

The ToC sponsonsorship was always very disturbing. Intentionally or otherwise, the sponsorship of cycling has to have acted as an EPO marketing tool. It raises the horrible possibility that cyclists could be used to fill a dual role, as both celebrity product endorsers and guinea pigs for the anti aging industry.

People talk about legalizing doping and ask why not? Legalizing sports doping is effectively giving carte blanche to off label drug use, on people who aren't even sick. IOW, healthy people would be treated like guinea pigs, without any of the potential population health benefits that provide the ethical justification for normal drug safety trials.

This is why, to date, I've refused to watch the ToC, even though it's one of the few races on during daylight hours in NZ. I just can't support the idea of EPO manufacturers sponsoring bike races.
 
Aug 27, 2012
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Sorry I should have been clearer.

Lance's cancer was diagnosed in 1996. It is likely that this developed as a result of the drug cocktails Eddy's program was experimenting with. Eddy got involved with Thomas Weisel around 1988. Eddy picked up Lance around 1990-1992 or so as part of the under 23 junior program.

So it's even more cynical. Once Lance overcame cancer and returned to cycling, he and Thom decided to leverage that into a great Cancer Jesus story. And Amgen also benefited from the cancer branding and exposure.

At the same time, around 1997, SCA were contracted to pay multiple millions for TdF wins, which just left UCI to take care of the "no positives" as proof of no doping as per SCA contract. And some well placed friendships and payments (read Hein) would take care of that.
 
May 14, 2010
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I Watch Cycling In July said:
This info adds some more context to Dim's diagram which connected the Weasel and Amgen. Amgen doesn't seem to have followed all the rules (surprise).

The ToC sponsonsorship was always very disturbing. Intentionally or otherwise, the sponsorship of cycling has to have acted as an EPO marketing tool. It raises the horrible possibility that cyclists could be used to fill a dual role, as both celebrity product endorsers and guinea pigs for the anti aging industry.

People talk about legalizing doping and ask why not? Legalizing sports doping is effectively giving carte blanche to off label drug use, on people who aren't even sick. IOW, healthy people would be treated like guinea pigs, without any of the potential population health benefits that provide the ethical justification for normal drug safety trials.

This is why, to date, I've refused to watch the ToC, even though it's one of the few races on during daylight hours in NZ. I just can't support the idea of EPO manufacturers sponsoring bike races.
The Amgen sponsorship could be seen as brazen, or as honest, or as both brazen and honest. Since honesty isn't their lingua franca, though, I'm going with just brazen.

Armstrong bragged of having a strong hand in helping organize ToC. I wouldn't be particularly surprised to hear the Amgen sponsorship was his idea. I can picture his pitch to them . . .

LA: Listen, you guys should sponsor this race. It's perfect for you in so many ways!

Amgen: Lance, you can't be serious! How could we possibly do something so public, so brazen? It would be suicide for us.

LA: Suicide? Are you kidding? Look at me - I'm clean! [laughter ensues] I'm not joking. Put on an anti-doping clinic, sponsor my cancer foundation - you'll reach everyone you want to reach - especially the riders and teams, but also the docs and the fans - with every message you want to send, and you'll look great doing it. The military guys call something like this a "force multiplier" - you can't miss!

Amgen: Lance Armstrong, you are a marketing genius!

Tinman said:
Sorry I should have been clearer.

Lance's cancer was diagnosed in 1996. It is likely that this developed as a result of the drug cocktails Eddy's program was experimenting with. Eddy got involved with Thomas Weisel around 1988. Eddy picked up Lance around 1990-1992 or so as part of the under 23 junior program.

So it's even more cynical. Once Lance overcame cancer and returned to cycling, he and Thom decided to leverage that into a great Cancer Jesus story. And Amgen also benefited from the cancer branding and exposure.

At the same time, around 1997, SCA were contracted to pay multiple millions for TdF wins, which just left UCI to take care of the "no positives" as proof of no doping as per SCA contract. And some well placed friendships and payments (read Hein) would take care of that.
Voila!
 
Aug 27, 2012
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Tinman said:
At the same time, around 1997, SCA were contracted to pay multiple millions for TdF wins, which just left UCI to take care of the "no positives" as proof of no doping as per SCA contract. And some well placed friendships and payments (read Hein) would take care of that.
And not only the $125k Sysmex payment, but also the $500k Weisel directly paid to UCI... http://www.cyclingnews.com/news/kathy-lemonds-sca-deposition-details-revealed

A Fed case re-opening would be interesting...
 
I don't see that much new here. The author of the book has focused on the length these companies went to to sell more drugs, the athletic side seems to be more of an intro.

In Europe, EPO's clinical trials began, and marathon runners, Nordic skiers and Dutch cyclists were getting a hold of the drug on the black market. From 1987 to 1990, about 18 young cyclists died under mysterious circumstances, including 27-year-old Johannes Draaijer. He had finished 20th in the 1989 Tour de France and had competed in another race a few months later. Then, he died suddenly of a heart blockage. It wasn't clear if Draaijer had used blood-thickening EPO. But his widow told the media that she hoped her husband's death would warn other athletes about EPO's danger.
The allegations here are probably not researched beyond google by the author. I think we have tried in the clinic, and only a few of the cyclist deaths could be linked to epo IIRC. The Nordic skiers part, stems from a comment by a danish dude I think, but nobody in the media followed it up. If there was anything strange going on with the Swedish skiers back then, I think we would know more about it.

Now the real crime here is pushing huge, perhaps lethal doses of epo on sick people to make money. And also the methods the drug companies used. I think all this is more of a problem in the US than most other 1st world countries. The US has a myriad of health systems, providing ample opportunity for exploitation. Countries with single payer systems don't have the same extent of these problems.

As far as I understand it EPO is difficult and expensive to synthesize. There was a quick program on it on Norwegian TV relating to the Armstrong case, and a professor said that it was very expensive and synthesized with the help of Hamster wombs.

This has perhaps changed in the last 10 years, with new drugs and new production methods.

Anyway, the point is that the drug is/was both expensive to produce and to get approval for by the regulatory authorities. Most drugs today are cheap to produce but expensive to research and get approval for.

So the dynamic of the profit making by the companies is a bit special with epo.

Now what also must be remembered is that one has to look at this in a historical perspective. Things are qualitatively different over the periods 1980-1990 1990-2000 and 2000 until now. Both in what companies can get away with regarding sales/marketing/fraud and what they can get away with regarding clinical trials etc.

And there is a huge difference between the US and the rest of the developed world due to the dysfunctional US health system. So things true for the US should not be seen as true of other places.

Now in the 80s we had the cold war, and sport had also become part of the cold war. What might not be that well known is that the Pentagon/CIA has a history of developing and testing drugs for different purposes, some for questionable uses and some not. However they have been careful to make sure most of the questionable testing is done outside of the US on non US citizens. The questionable research is usually buried, but some things were so big or badly hidden that they have come to the surface in some way.

It would not surprise me that much if some of the epo testing was done on athletes at the behest of the Pentagon in the late 80s. Soldiers on the battlefield sometimes need enhancement, and athletes are a good group with which to see if an effect is beneficial.

Now, I'm pretty sure most of the egregious clandestine pentagon medical research ended with the cold war in 1990-91, or shortly after. Mind you, I'm not 100% sure of any clandestine activity going on in the 80s. But it would fit a pattern of programs getting smaller and more hidden from the 40s an onward. The later the program, the more elaborately hidden and smaller.

Then came the period when the drug companies could exploit the regulatory and health systems to make money. This took on huge proportions in the US were there are several payers to rip off. However this also happened in Europe to some extent. Though the effect of this fraudulent behavior is likely to differ in regards to how corrupt these countries are(cough Greece:D).

Since 2000 there has been increased focus on the regulatory frameworks all over the world. The US with it's myriad of systems has a lot to clean up.

So when thinking about Amgen and other companies involvement in doping, it is important to remember that the opportunity for involvement is different over the different time periods. And, that the situation in one country can not be easily transferred to the situation in another country.


PS. I'm no expert. This is all my opinion on how things are/ might have been in the past.
 

mastersracer

BANNED
Jun 8, 2010
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Maxiton said:
It could be that Amgen is merely the innocent manufacturer. In which case it certainly isn't their fault that their honest drug has been misappropriated for misuse and abuse by athletes. The fact that the principle investor and instigator/mentor behind Armstrong & team is also a principle investor in the manufacturer of EPO, Amgen, could simply be a curious coincidence. The fact that a so called black market in EPO developed among Euro athletes just as trials started for the drug in Europe could also be a coincidence. The fact that this black market developed at a time when Amgen was under pressure to find markets for the drug and move as much of it as possible - that, too, could be a coincidence. The fact that the drug found its way to Weisel's team - yet another coincidence. So many coincidences! Remember the "magic bullet" theory of the JFK assassination? This drug is like that. EPO and its spectacular coincidences are the magic bullet of the peloton, and Amgen/Weisel are innocent bystanders. OR . . .

Amgen and a principle investor, Weisel, identified competitive sport as a potentially huge avenue for profit, especially once they had taken a most unlikely canditate for sporting success - former cancer patient Armstrong - and used their drug to transform him into sporting superman. How far would they go to make this happen and maintain it? For the answers, you'll have to ask them. Or maybe we can just wait and let the investigators ask . . . .
Conspiracy theories are plausible if you don't have any facts. Amgen's agreement with J&J gave Amgen exclusive rights to sell the drug for renal anemia. This is a $3 Billion market in the US alone. They were willing to give J&J all other uses because capturing renal anemia market share would be a home run for the startup. The notion that the company pinned their ROI hopes on an emerging black market among professional athletes doesn't make sense. What size - at best - is that market? Why would Amgen not care about EVERY OTHER legitimate medical market re the J&J deal? The answer is simple: because renal anemia was a big enough market.

Amgen entered the ToC sponsorship deal once it realized it had misses an enormous market: anemia in chemotherapy patients. They did it to promote their 'breakaway from cancer' campaign to compete against J&J and increase sales of Aranesp. 75% of cancer patients experience anemia - consider the size of that market compared to at most a few hundred or thousand athletes. Suggesting they did this to market the drug to athletes as a PED is ridiculous given the potential markets of these alternatives.
 

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