Re: Farmyard drug store
Here's the full text. BTW, I more than doubled my GTCB holdings recently with an average new purchase price of $1.31.
The farmyard drug store
Pharmaceuticals made in genetically modified animals have been poised to take off for years. Heidi Ledford investigates the reality.
The birth of Herman the transgenic bull in 1990 was supposed to herald the start of a new era in pharmaceuticals. As a bull, Herman failed spectacularly in his main job: to produce an iron-rich human protein called lactoferrin in milk. Even his offspring produced disappointingly low levels of the protein.
But hopes have been renewed by Sweetheart, a transgenic goat who lives in Massachusetts, on a farm run by Framingham-based GTC Biotherapeutics. On 2 August, the anti-clotting agent in Sweetheart's milk, ATryn, became the first drug produced by a transgenic animal to be approved by the European Medicines Agency (EMEA). Two weeks later, Pharming Group — a descendant of the company that created Herman — announced that the EMEA had accepted its application to market an anti-inflammatory drug produced in transgenic rabbits.
The farmyard may seem alive with drug possibilities these days, but the field is still struggling. Sweetheart's success is the first after a series of failures, and some analysts argue that major industry players have lost interest altogether in the pharmaceutical promise of transgenic animals.
"The industry has been holding its breath for over a decade for a product to be approved by the Food and Drug Administration or EMEA," says Willard Eyestone, professor at the Virginia-Maryland Regional College of Veterinary Medicine in Blacksburg, Virginia.
Enthusiasm was far higher in the early 1990s, when drug companies first started to focus on biopharmaceuticals — products made from large biological molecules such as proteins and antibodies. Proteins are typically produced in giant vats of cultured mammalian cells, and the process can be difficult and expensive. So making pharmaceutical proteins in transgenic farm animals — sometimes called 'pharming' — was hailed as a way to drive down production costs while boosting volume.
Sweetheart, for example, can be milked using standard dairy equipment; the protein is then purified and dried to a white powder. Maintaining her is a matter of feeding and milking. Need to scale up production? Breed more Sweethearts. The cost of using transgenic goats has been calculated to be anywhere from 3 to 100 times less than cell-culture processes.
Biopharmaceuticals is now a US$33-billion industry, but transgenic animals have yet to play any part in it and pharming companies have had a difficult history. In 2001, PPL Therapeutics of Edinburgh, UK — an offshoot of the group that created Dolly the cloned sheep — brought a pharming drug called alpha-1-antitrypsin to clinical trials. The drug, produced in sheep's milk, was meant to treat lung disorders. But reports of wheezing among patients prevented the drug from advancing to phase III trials. The company folded two years later. Its competitor, Pharming, nearly went broke around the same time, after deciding to switch from rabbits to cell culture for production of another drug. It has since stabilized as Pharming Group, based in Leiden, the Netherlands.
Animal crackers
The turmoil created a negative image of the transgenic animal market. "You've got one company running out of money and the other running into regulatory trouble," says Harry Meade, vice-president for research and development at GTC. "It certainly gave us pause. We were the last dog standing." GTC struggled too; its stock currently hovers around $1.50 a share, down from a high of nearly $50 in 2000.
Today, the pharming landscape is speckled with a few small companies. Venture capitalists have largely shied away from the technology, and bigger pharmaceutical companies have not embraced it either.
Pharming Group probably faces a tough road even if its latest product achieves regulatory approval, says Marcel Wijma, senior equity analyst at SNS Securities in Amsterdam. The company's drug, Rhucin, is targeted at people who have hereditary angioedema, a painful and sometimes fatal condition that causes severe swelling in various body tissues. The condition affects only 30,000 people in the Western world. Three other companies are also developing drugs for the condition; Pharming Group is the only one working with transgenic animals.
GTC
Even if Pharming wins 40% of the hereditary angioedema market, Wijma estimates that it would not make more than $100 million to $250 million a year. Couple this with the predicted $50 million that GTC could make with ATryn, and drugs produced from transgenic animals would be a mere drop in the $33-billion ocean. Both companies are planning clinical trials for other uses of their drugs, however, which could expand their potential. Navdeep Jaikaria, a biotechnology analyst at Rodman & Renshaw in New York, suggests that GTC could make up to $250 million a year from ATryn, if it were able to market it for a range of clotting disorders. The EMEA approval currently covers its use for only very specific cases of a hereditary disorder.
And the expense of biopharmaceuticals means pharming drugs is still attractive, says Jaikaria. It costs $10,000 a year, for instance, to treat an anaemic dialysis patient with Epogen, a recombinant form of human erythropoietin. Pressure from health-insurance companies, Jaikaria argues, will push the industry to take another look at farmyard pharmaceuticals.
Culture shock
Competing technologies have advanced in the meantime, however. Peter Knight, an analyst at Wood Mackenzie in Edinburgh, points to the pharmaceutical company Wyeth, based in New Jersey. Wyeth recently created a cell-culture system that can generate 9 grams of protein per litre of culture. Just four years ago, its standard was 1 gram per litre. So cell-culture yields are catching up with production rates from transgenic animals, which typically yield between 1 and 10 grams of protein per litre of milk.
"Pharming is certainly a technology that five years ago was attracting a huge amount of interest," says Knight. "But it does seem to have lost ground to other methods."
Competition is also provided by transgenic plants, Knight adds. Like animals, plants can be engineered to produce therapeutic antibodies and vaccines. Admittedly, it is harder to stop transgenic lines escaping into the environment, and there is a greater chance that proteins made in plants will provoke adverse immune responses in humans. But they promise shorter production times and a lower probability of contamination by viruses or prions.
Big companies, such as Indianapolis-based Dow AgroSciences and Swiss firm Syngenta, are already backing pharmaceutical production in plants. In fact, the next transgenic drug expected to gain EMEA approval is CaroRX, a product from California firm Planet Biotechnology that stops a cavity-causing bacterium from sticking to teeth.
Meanwhile, companies such as GTC and Pharming continue their slow march to the animal market. Interestingly, GTC's next big project is producing alpha-1-antitrypsin, the drug that caused PPL Therapeutics to fail.
Meade is undaunted by the drug's fraught history. "It's fair game," he says. "We've got goats that make 20 grams per litre."
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