While responding to a comment on the post about cancer drugs below, I did some research and ran into an eye-opening description of how most cancer drugs are developed. BeIow an excerpt from a piece by Dina Biscotta on the Longview Institute website (http://www.longviewinstitute.org/)
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The pharmaceutical industry promotes the idea that the market is responsible for innovations in medicine. . . . This statement obscures the enormous role that the federal government plays in the development of new drugs and therapies. The case of Taxol provides a compelling illustration of this pattern. Taxol is used most widely to treat ovarian and breast cancer and Kaposi’s sarcoma. . . .
Taxol is a complex compound found in the bark of the Pacific yew tree. The bark was first collected in 1962 and its potential for killing cells was demonstrated in 1964 as part of the National Cancer Institute (NCI)-United States Department of Agriculture (USDA) plant screening program.
In 1971, chemists at the Research Triangle Institute in North Carolina, a nonprofit research organization created in 1958 by leaders in academia, business and government, first isolated the compound. The NCI selected Taxol as a development candidate in 1977 and clinical trials began in 1984. The yew bark was supplied by the Natural Products Branch of the NCI, sourced from trees located on National Forest lands. In 1989, the Johns Hopkins University Oncology Group reported that Taxol produced a very high response rate in women with ovarian cancer whose cancer had been unresponsive to other chemotherapeutic agents.
In December 1989, the NCI chose the pharmaceutical giant Bristol-Myers Squibb as its partner in a Cooperative Research and Development Agreement (CRADA) to work on Taxol. This agreement gave Bristol-Meyers Squibb exclusive rights to develop Taxol for the commercial market and exclusive rights to all clinical data generated by the NCI from trials it had or would undertake to study the drug’s effectiveness. Bristol-Meyers Squibb also got the right of first refusal on all yew products on Federal lands as well as orphan drug status which allows firms up to 7 years exclusive marketing rights over a drug that has not been patented.
(One might wonder why the government gave all of this to Bristol-Myers . . . . I can only imagine how much Bristol must spend on lobbyists and campaign contributions . —MM )
Sales of Taxol in 1992 were $50 million, and they rose to $580 million in 1995. This represented one third of Bristol-Meyer Squibb’s anti-cancer drug sales in that year. This pattern of the government doing most of the work while the pharmaceutical company reaped the rewards arose from the reluctance of firms to invest in the development of new cancer drugs. Research and development costs are enormous and the return in terms of successful drugs is particularly small. For these reasons the government took over the direction of cancer research, including the search for new drugs.
(Note: the government is interested in the public good–trying to find a cure for cancer. For-profit corporations are not; it's too risky, and too expensive. So they focus their research on “me too” drugs for common conditions like allergies, and let the government do the costly research. Then they claim that they have to charge exorbitant prices because they spend so much on drugs that fail. In fact, drug-makers spend more on marketing advertising than they do on research. MM)
The National Cancer Institute was established in 1937, and in 1953, the NCI, directed by Congress, initiated a national program of chemotherapy research, which led to the establishment of the Cancer Chemotherapy National Service Center (CCNSC) in 1955. The CCNSC facilitated collaboration between pharmaceutical companies in the collection, synthesis and testing of chemical compounds for anticancer activity. The program generated the world’s largest computerized database for experimental drugs. “In its ‘war against cancer’ (declared by President Nixon in 1971) the US state has (since the mid-1950s) funded and also managed, not just the relevant basic research but also applied research, development, formulation, toxicity testing and clinical trials of many new disdrugs—that is, all the R&D necessary to take a potential drug almost to the point of full scale production and market launch—in complete contrast to the [pharmaceutical industry’s ideology of “minimum government intervention and relying on market forces to e]nsure the appropriate allocation of resources. ”
(I would add only that the taxpayer is paying for these drugs twice: first he funds the research, then he forks over billions to buy the product form the pharmaceutical industry. In a rational world, the government would finish the research it started—or contract with a non-profit to do so at a reasonable price. Drug companies might be hired to distribute the drug, but it if was effective and truly a breakthrough, no huge marketing campaign should be needed. The information could be disseminated through medical conferences and medical journals, which should be very selective in what they write about. There are far too many new drugs on the market. –mm)
Sources:
Walsh, Vivien and Jordan Goodman. “ Cancerchemotherapy, biodiversity, public and private property: the case of the anti-cancer- drug Taxol.” Social Science and Medicine. 49 (1999) 1215-1225.
Walsh, Vivien and Muriel Le Roux. 2004. “Contingency in innovation and the role of national systems: Taxol and Taxotère in the USA and France” Research Policy. 33 (2004) 1307-1327.
“In a rational world, the government would finish the research it started—or contract with a non-profit to do so at a reasonable price.”
Maggie,
Why don’t they?
You’re leaving out a key part of the story. Robert Holton was the key to Taxol. Its not cost effective to harvest yew tree bark for mass distribution. The yew tree has only a limited growing range, you need a synthetic pathway in order to mass distribute Taxol.
Holton was the key to discovering the synthetic pathway, that allowed Taxol to be created in a lab instead of a farm. He was closely affiliated with Bristol. Without Holton, Taxol never gets produced.
Joe Blow-
Holton did not work for Bristol. Bristol deserves no credit for his work.
Yes ” late 1989, Holton’s group had developed a semisynthetic route . . .Florida State University, where Holton worked, signed a deal with Bristol-Myers Squibb to license this and future patents.In 1992, Holton patented an improved process with an 80% yield.”
Why didn’t Florida State come to the National Cancer Institute with its research? Why did the go to Bristol-Meyers instead?
Greed.
Ten years earlier, universities that did medical resarch kept their distance (“arms-length”) from for-profit corporations.
Former Harvard President Derk Bok has written a book about the corruption of universities in this regard.
Note that Jonas Salk never considered getting a patent on his vaccine. Holton was eager to get a patent.
Barry–: In a rational world, the government would finish the research it started—or contract with a non-profit to do so at a reasonable price.”
And you ask: “Why don’t they?
Becase our legislators depend on campaign contributions to keep their jobs. The people who can afford to make huge
campaign contributions are
corporations and shareholders.
This could change. Obama won the election with a huge number of very modest
contributions.
Combine with some campaign reform (shorter, less expensive elections/) and we could have a Congress that represents the public inter st rather than coporate and wealthy shareholder interests.
I wrote
Actually, it was Arthur S. Barclay, a 32-year-old Harvard-trained botanist working for the U.S. Department of Agriculture in 1962, who is credited for finding what was to become Taxol. He had been sent out West to collect samples of trees, shrubs, weeds, seeds (anything in the plant kingdom) for a government program aimed at finding natural chemicals that might be of some use as medicines. Barclay’s quest was a bag of samples pulled from the Pacific yew tree.
By 1988, developing Taxol had cost the NCI over $25 million. Other promising compounds were getting squeezed out of the competition because of this single, impossible-to-get molecule. The governement was eager to find a deep-pocket pharmaceutical company willing to take a chance on turning Taxol into a marketable drug.
Thanks to a novel tool Congress had created vis the Federal Technology Transfer Act of 1986, it handed over the commercial rights to Taxol, a substance found and then preened all the way to the market’s front door by taxpayer dollars to any private company the NCI chose.
In August 1989, a Cooperative Research and Development Agreement (CRADA) grant was given to Bristol-Myers, soon destined to merge with Squibb. It helped that the company had built a good track record in working with the feds on a previous drug, DDI, and early treatment for AIDS.
Handing the keys to Taxol, Bristol consolidated control over the entire Yew bark collection and compound extraction apparatus, picking up the NCI’s contract with Hauser Chemical Research Corporation, and on April Fool’s Day, 1990, the company signed a contract that changed forever the future of Taxol.
Bristol-Myers Squibb was handed an exclusive licensing agreement to use Bob Holton’s spanking new semisynthesis patent plus any related patents that his research might cook up over the next five years. In exchange, Florida State University was entitled to royalties on any money Bristol made using any of its Taxol patents, and Holton got a five-year research collaboration deal with Bristol chemists worth $1.7 million.
In January 1993, Taxol (officially trademarked as a Bristol product) made its debut in cancer pharmacology. From bark to business, the molecule’s development had taken 31 years and had cost the government roughly $32 million. Before 1993 ended, a single gram of Taxol was selling for $5,846. Taxol was hobnobbing with the priciest potions ever made.
As a cancer-fighter, Taxol was not all that rosy. The drug had some serious drawbacks. For hundreds of cancer patients, the drug simply bounced off their tumors, doing little if any good. Side effects were a real headache too. Taxol’s castor-oil carrier was suspected as the culprit behind much of the misery, which included nausea, vomiting, joint pain, appetite loss, brittle hair and tingling sensations in hands and feet. People soon began to realize that the much ballyhooed drug was no panacea.
But the sales of Taxol began to grow exponentially, and by 1995 the drug was the hottest selling cancer medicine on the planet, passing half a billion dollars in revenues that year. BMS would see an average of 38% annual growth in sales of its blockbuster drug for the next seven years, until sales peaked in 2000 at nearly $1.6 billion.
From: A Tale of Taxol, Florida State University
Gregory–
You write that by 19988 “The governement was eager to find a deep-pocket pharmaceutical company willing to take a chance on turning Taxol into a marketable drug.”
This suggets that the govenrment needed a for-profit drug maker (in this case, Bristol Meyers) to bail it out. (Given the second half of your post, I don’t think that this is what you meant to say , but this is what you seem to imply.)
The fact is that a medical researchet at Florida STate — a Public University, funded with taxpayers dollars– was able to figure out how to synthesize the drug without depending on the tree bark.
So why didn’t Florida State come to the NCI with its research? And why did the gov’t give the whole thing over to Bristol-Meyers?
As you point out,Taxol didn’t turn out to be what patiens hoped for. Nevertheless, it reaped huge profits for the company.
In August 1989, when NCI wanted to get out of the Taxol business (there was simply no way the government could justify the enormous costs of keeping Taxol in the pipeline), it advertised a grant to give out and four companies rose to the bait, including Rhone-Poulenc (which held the French Taxol patents) and Bristol-Myers. In other words, the government was eager to find a deep-pocket pharmaceutical company willing to take a chance on turning Taxol into a marketable drug.
Although FSU officials didn’t know it at the time, they had brokered the deal of a research university’s lifetime. Bristol was handed an exclusive licensing agreement to use Bob Holton’s spanking new semisynthesis patent plus any related patents that his research might cook up over the next five years. In exchange, FSU was entitled to royalties on any money Bristol made using any of its Taxol patents.
FSU also got Bristol to agree to cover all costs associated with patenting anything Holton’s lab came up with, including Taxol derivatives, some of these derivatives (analogs) might even prove to be better cancer-killers than the mother molecule itself.
In 1992, shortly after Taxol won FDA approval for use against ovarian cancer (with only 30% efficacy), FSU patented a vastly improved version of his original semisynthesis. Known as the metal alkoxide process, the method produced an overall yield of better than 80%. An easier, more cost-efficient way to scale up the drug’s synthesis using material extracted in bulk from the needles of the English yew.
In regards to Taxol not turning out to be what patients hoped for, in 2004, using a technique that quantified circulating tumor cells, German investigators from Friedrich-Schiller University in Jena, had shown that neoadjuvant chemotherapy with Taxol caused a massive release of cells into the circulation, while at the same time reducing the size of the tumor. In three different Taxol-containing regimens, as the tumor collapses (a clinical response), it produced the greatest degree of tumor shrinkage but also the greatest release of circulating tumor cells.
Even before that, it had been observed in various cell-death assays that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from Taxol therapy, even in cases where the majority of the cells are being killed by Taxol. It may indeed give clinical response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to Taxol are often dramatic. Taxol helped caused the demise of my wife.
This excellent Fortune article tells the story.
http://money.cnn.com/magazines/fortune/fortune_archive/2005/09/19/8272884/index.htm
http://www.medicynic.com
“Why didn’t Florida State come to the National Cancer Institute with its research? Why did the go to Bristol-Meyers instead?”
When’s the last time hte NIH mass produced anything, whether it be a vaccine or a drug? The NIH/NCI arent in the business of mass producing anything. If FSU went to the NCI as you suggest they should have, they would have told them to open up a partnership with big pharma.
The goal of the NIH/NCI is to fund basic science research, not develop mass production pipelines for promising candidates. They arent interested in that job and arent funded or have the infrastructure to do it.
Maybe they should change their mission focus, but thats how things stand now. The director of the NCI is not exactly screaming about being left out of the mass production process.
A very parallel protocol was involved with Gleevec by Novartis as well.
Hi Everyone…
Great information for Drugs.
All the stories about Taxol, Gleevec and the other cancer drugs that arose from the National Cancer Institute’s far-reaching drug development program are contained in “The $800 Million Pill” in a chapter entitled “The Failed Crusade?”
Merril–
Thanks for the head’s up.
Your book is sitting on my bookshelf next to my desk–I should have looked at it.
But I read it several years ago, and forgot that whole section about Taxol
Merrill provides more detail which confirms that taxpayers were robbed while patients were gouged.
He points out that when NCI contracted with Briston-Myers, the contract said that the company would sell the drug at a “just and reasonable price”. (The company went on to sell it for $10,000 per course of treatment
Moreover, the first draft of that contract said that the government “will receive a reasonable share of income once the drug is martketed for general use.”
That clause was later elminated from the contract. Why? Some accused NCI of being “too cozy” with Bristol.
NCI had taken the drug to a point where clnical trials showed that the drug shrunk tumors–and sometimes eliminated them–in humans.
Thus Bristol was not taking much of a risk that the drug would prove totally ineffective.
Just what did Bristol contribute? They manufactured and distributed it.
Merrill quotes Joseph Rubinfield who ran Bristol’s oncology division from 1968 to 1980: “Bristol never invented anything themselves but they were great developers . . .They took the jobs that somebody else had done, especially NCI, and commercialized them.”
Goozner points out that some drug firms did contribute to research and invested money in products, but others came in “when the new drug was well along in clnical trials” overseen by the government. Sometimes the drug company spent next to nothing to become a partner.
But the companies almost always managed to price cancer drugs so that they could turn a very nice profit–and the prices kept spiralling higher and higher.
To find out more, I urge you to buy Merrill’s book: The $800 Million Pill. .
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