FDA approves medicine from engineered goats

Potentially opening a new era in farming and pharmaceuticals, the U.S. government has approved the first drug produced by genetically engineered livestock.

The drug, meant to prevent fatal blood clots in people with a rare condition, is a protein extracted from the milk of goats that have been given a human gene.

The same drug, which was approved in Europe in 2006 but has not been widely adopted, is the first to have been cleared by the U.S. Food and Drug Administration under guidelines the agency adopted only last month to regulate the use of transgenic animals in the nation's drug and food supply.

Made by GTC Biotherapeutics, the drug is produced by a herd of 200 goats that live under quarantine on a high-security farm in central Massachusetts. The animals have been bred to contain a human gene that causes their milk to produce a human blood protein that can be extracted and processed into the anti-clotting drug.

Proponents say such animals could become a way of producing biotechnology drugs at lower cost or in greater quantities than with the existing methods, which involve extracting the drugs from donated human blood or growing genetically engineered cells in steel tanks. The protein in the goat milk, antithrombin, is sometimes in short supply or unavailable for pharmaceutical use because of a shortage of human plasma donations.

GTC Biotherapeutics said one of its goats can produce as much antithrombin in a year as can be derived from 90,000 blood donations. And if more drug is needed, the herd can be expanded.

"If you need more, you breed more," said Thomas Newberry, a spokesman for GTC, which is based in Framingham, Massachusetts.

Other drugs produced in animals are under development. One company, Pharming, based in the Netherlands, plans to apply this year for U.S. approval of a drug produced in the milk of transgenic rabbits to treat hereditary angioedema, a protein deficiency that can lead to dangerous swelling of tissues.

Another company, PharmAthene, working under a U.S. Defense Department contract, is developing a treatment for nerve-gas poisoning in the milk of transgenic goats.

But turning animals into walking pharmaceutical factories does not sit well with some environmental advocates and animal rights activists.

"It is a mechanistic use of animals that seems to perpetuate the notion of their being merely tools for human use rather than sentient creatures," the Humane Society of the United States says in its position paper on the practice.

There are also more concrete concerns - that the animals could be harmed, that animal germs might contaminate the drug, and that the milk or meat from genetically engineered drug-producing animals might enter the food supply. There is also a concern that such animals might escape and breed with other animals, spreading the gene, with unpredictable consequences.

Still, it is not clear to what extent the use of the animals will catch on. Established manufacturers might stick with the tried-and-true methods.

"I think we have very good ways of making therapeutic proteins today," said Norbert Riedel, chief scientific officer at Baxter International, which makes proteins both from human plasma and in cell culture. One risk of using animals is that drug production can be lost if a disease wipes out the herd.

Still, the government's stance on the GTC drug, which was issued Friday, eliminates one barrier to producing drugs in animals: companies' uncertainty over whether the Food and Drug Administration would ever approve such a drug.

"It really takes away one of the biggest issues that have always been on the table, which is how do regulatory agencies view this kind of technology," said Samir Singh, president of the U.S. operations of Pharming.

Indeed, showing that approval could be obtained is a major reason GTC developed its drug, ATryn. Sales of the drug are expected to be modest. It was approved in Europe in 2006, and sales there have been small.

ATryn will be sold in the United States by Ovation Pharmaceuticals. It is not clear what the price will be and how that price will compare to that of the product from human plasma. The drug was approved for people born with a rare hereditary deficiency of antithrombin to prevent blood clots while they undergo surgery or childbirth.

People with the deficiency are vulnerable to blood clots. They can reduce that risk by taking blood thinners like warfarin. But during surgery or childbirth, blood thinners are usually not used because they increase the risk of excessive bleeding.

The FDA determined ATryn was as effective as antithrombin derived from human plasma in preventing clots. However, the protein derived from plasma lasts longer in the body than the one from goats, probably because the sugars coating the protein are different.

To make its protein, GTC took the human gene for antithrombin and linked it to goat DNA that normally controls production of a protein found in milk. That insured that the antithrombin would be produced only in the milk.

The gene was injected into a one-celled goat embryo, which was then implanted into the womb of a surrogate mother. If it were doing it today, GTC would implant the gene into a skin cell of a desired animal and then produce a clone, a more reliable technique. But Dolly the sheep, the first cloned mammal, had not been created when GTC started its work in the early 1990s.

Once GTC had produced a goat with the human gene that produced the antithrombin in its milk, that "founder" animal was mated with others through conventional breeding to start producing a herd.

Many of the newer protein-based drugs, such as the cancer drugs Avastin and Erbitux and the arthritis drugs Enbrel and Humira, are produced in genetically engineered Chinese hamster ovary cells that are grown in big stainless-steel vats.

But a cell culture factory can cost hundreds of millions of dollars to build. Using livestock eliminates all that steel and shrinks the investment to tens of millions of dollars, said Geoffrey Cox, chief executive of GTC.

One drawback is that given the generation and gestation times of animals, it can take 18 months to start getting protein production from a goat, compared with a few months for cell culture.

http://www.iht.com/articles/2009/02/08/business/drug.1-424973.php?page=2

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