Doubts over 'pharming' technology

Some proteins can only be made in mammalian cells

By Dr David Whitehouse BBC News Online science editor

Doubt has been cast on the potential for using genetically modified animals as pharmaceutical factories.

There have been doubts growing about the viability of transgenic animals for some time

Sally Bennett, ING Barings

It follows the announcement of a delay of at least two years in the testing of the drug that was aiming to be first "pharmed" product to market. Analysts said there were now serious questions being asked about the future viability of the sector.

The decision of PPL Therapeutics - the Scottish biotechnology company that owns the technology behind Dolly the sheep clone - to push back the commercial launch of AAT (alpha-1-antitrypsin) has prompted a crisis of confidence in investors.

The reason for the delay in the drug, designed to treat lung diseases, was said to be due to patients "wheezing" in clinical trials.

Necessary stage

For more than a decade, it has been possible to make pharmaceutically useful human proteins in genetically modified bacteria. Insulin, for example, is now produced in vast quantities in this way.

But some human proteins are either too large or too complex for microbial cells to synthesize. PPL has the patent on technology that will drive the production of human proteins in the milk of sheep and other farm animals.

And allied to cloning, this should allow PPL to set up whole flocks that can be pharmed for human proteins in an economically viable way.

PPL currently has a number of transgenic sheep producing alpha-1-antitrypsin, a protein which sufferers of several lung diseases - notably hereditary emphysema and cystic fibrosis - lack. A drug made from this sheep-produced human protein is now in clinical trials, a process that must be completed to satisfy regulators the product is both safe and effective.

But PPL has said it will now have to conduct further investigations before it can take the drug into the final stage of the trials. This means AAT is unlikely to reach the market before 2007, two years later than expected.

Patients drop out

The setback is the latest in a series of problems for PPL. Julie Simmonds, an analyst at Beeson Gregory, said: "PPL are going backwards rather than forwards. My concern is that there is a fundamental problem with the technology."

PPL's chief executive Geoff Cook said: "It is certainly a disappointment. But the most important thing to make sure of is that when we do go into the next phase of trials, we go with absolute belt and braces security.

"The regulators are extremely stringent, because this could be the first drug from transgenic animals to reach the market."

Last year, the US Food and Drug Administration told PPL that it had concerns about three patients who failed to complete a phase II trial of AAT.

Mr Cook said he understood they had dropped out because they suffered "extra wheezing", exacerbating a condition that is common in emphysema. PPL said it could be linked to the dosage or purity of the drug, or to an inhaler supplied by a partner company.

But initial analysis has failed to pin down the problems with certainty and now further investigations will be undertaken.

Growing doubts

Biotechnology analysts say there are now growing doubts about whether transgenic technology can work.

One of PPL's rivals, Dutch firm Pharming, went bust last year. Also, progress in work on transgenic animals by Genzyme in the US has been slow.

Analyst Julie Simmonds told BBC News Online: "My main concerns are around the fact that to date no transgenic products have reached the market - although quite a number have been in development for some time.

"This may just be the natural rate of attrition of pharma products - however, one would expect that proteins should be easier to develop, although final delivery to the patient may be more of a problem."

Sally Bennett, of ING Barings, said: "This is pretty significant bad news - they've had delay after delay. There have been doubts growing about the viability of transgenic animals for some time."