BioEd Online

An application to market a drug made in the milk of genetically modified (GM) goats was turned down this week. The decision means that, despite more than a decade of work using GM animals to produce drugs, no products have yet been approved for use.

GTC Biotherapeutics of Framingham, Massachusetts, has spent almost 15 years developing a herd of genetically modified goats whose milk contains a human anticoagulant called anti-thrombin. The company planned to market the drug under the name ATryn.

But the London-based European Medicines Agency (EMEA) turned down their request on 23 February, saying the product hadn’t been tested enough.

"It's important to stress that the grounds for refusal have nothing to do with the use of a transgenic animal," says Martin Harvey Allchurch, spokesman for the EMEA.

Easy breeding

ATryn was designed for people lacking a working anti-thrombin gene, who can have an increased risk of blood clots. At the moment they are given blood-thinning drugs such as Warfarin, but this can raise the risk of bleeding to death during childbirth or surgery. At such times anti-thrombin itself is used, the only present source of which is human blood.

GTC spokesman Tom Newberry says that goats' milk is an ideal place to make these proteins, because it can deliver large quantities relatively cheaply and reliably. Some therapeutic proteins are currently produced in bioreactors, huge brewing vats that typically contain cultured Chinese hamster ovary cells. But large, complex proteins such as anti-thrombin are difficult to make this way. And breeding goats is easier than building reactors.

GTC added a copy of the human anti-thrombin gene to a goat gene that makes milk. The engineered DNA was injected into an embryo, and a goat herd built up by conventional breeding. "Getting the protein into the milk is the easiest part," says Newberry. The difficult part is purifying the proteins and doing enough clinical trials, he adds.

Trial, trial again

The difficult part is purifying the proteins and completing sufficient clinical trials, Newberry says.

The EMEA recommended that GTC test their drug on 12 patients undergoing surgery. But the company only presented evidence from five cases, which the EMEA says is too few. Newberry says that the drug also tested positively during nine childbirths, but that the EMEA excluded these from the surgical tally.

The agency also pointed out that the marketed product would have an extra filtration step that was not included in the trials. Finally, they said that GTC had done too few studies to assess whether patients developed antibodies in response to ATryn.

The company plans to appeal against the decision.

Moo milk

Despite the setback, the next such application is just around the corner. Pharming, a biotech company based in Leiden, the Netherlands, is awaiting approval from the US Food and Drug Administration for an antibacterial agent called lactoferrin, which they produce in the milk of GM cows.

Samir Singh, chief business officer with Pharming, believes the company will get a positive response by the end of this year. As human lactoferrin would be a 'nutriceutical' — a food additive intended to boost health — it has fewer hurdles to clear than a drug.

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