Europe Rejects Genetically Engineered Drug
By ANDREW POLLACK
http://www.nytimes.com/2006/02/24/bu...ss/24drug.html
European regulators declined yesterday to approve what would have been the first drug produced in the milk of genetically engineered animals, dealing a setback to a fledgling industry that aims to convert cows, goats and rabbits into low-cost pharmaceutical factories.
The decision was closely watched because companies developing drug-producing animals need an approval from either the United States or Europe to persuade pharmaceutical companies to try the production method.
The drug's developer, GTC Biotherapeutics, said it would appeal the decision, adding that the ruling was based mainly on a problem with its clinical trial, not on the fact that the drug was made in goats.
"With a new technology there is a conservatism that is not inappropriate," Geoffrey F. Cox, chief executive of GTC, said in a conference call with analysts. But he added, "There is no way with this company and what we have achieved over 15 years that we will let this block us from getting the product to market."
Shares of GTC, which is based in Framingham, Mass., fell 90 cents, or 40 percent, to $1.35.
GTC and a few other companies put human genes into animals so they produce a human protein in their milk. The animals can be milked and the protein purified for use as a drug.
The companies say the method is a cheaper and easier way to produce biotechnology drugs. Many biotech drugs, like cancer-fighting monoclonal antibodies, are made in vats containing cultures of genetically engineered animal cells. Such factories can cost several hundred million dollars.
Other protein drugs, like the one GTC is developing, are extracted from donated blood, but are found in such minute quantities that they are often in short supply. GTC said it would take 90,000 blood donations to obtain as much of the protein as one of its goats can produce in a year.
But drug companies have been reluctant to use the technology, in part because they were unsure how readily regulators would approve drugs developed that way. So GTC decided to seek an approval by itself, even if sales of the drug would be small.
It tested an anticlotting protein called antithrombin on patients who have a rare inherited deficiency of the protein and are at risk of potentially fatal blood clots. The company tested the drug on 14 people who were undergoing surgery or giving birth. At those times, because of the risk of bleeding, such patients cannot take the blood thinners they usually use to prevent clots.
The European Medicines Agency said yesterday that its advisory committee recommended against approval because too few patients undergoing surgery were tested. Also, the drug tested was not made in exactly the same way as the drug that would be sold, because a filtration step was added after the trial began.
GTC executives said the committee decided not to count pregnant women included in the test, because the dosing of the drug was not optimal. They also said the regulators had concerns about possible immune reactions to the drug, though none were seen.
The company is doing another trial aimed at applying early next year for approval in the United States.
Another company, Pharming, has asked the Food and Drug Administration to certify its human lactoferrin protein, made in transgenic cows, as "generally recognized as safe." That designation would allow Pharming to sell the protein for use in food products. Human lactoferrin is naturally found in mother's milk.
Pharming, a Dutch company that has recovered from a financial collapse a few years ago, is also in late-stage clinical trials of a protein called C1 inhibitor, produced in rabbits, to treat hereditary angioedema.
PharmAthene, based in Annapolis, Md., is trying to win a contract from the Defense Department to supply a protein, butyrylcholinesterase, to help treat people exposed to nerve gas. The protein is found in blood plasma but in such small amounts it would be impossible to make as much as the military needs, the company said.
"It would take approximately 500 liters of plasma to produce a single dose," the company's director for education, Stacey Jurchison, said. "We have about 250 goats. The milk they would produce in a year's time would be sufficient to produce 100,000 doses."
Production of drugs in transgenic animals is not the only part of barnyard biotechnology that has suffered setbacks. So has cloning, which involves making copies of desirable animals, rather than putting foreign genes in them. The F.D.A. has continually put off making an expected decision that the meat and milk from cloned animals and their offspring are safe to consume.