GTC stuck with goats because they reproduce more rapidly than cows and can yield more protein than mice or rabbits. Other efforts, including a more nascent GTC endeavor, have opted for cows. Pharming, a Netherlands-based company, aims to milk both cows and rabbits for drugs. Yet others have pursued distinctive forms of bioreactors: making drugs in chicken eggs, for instance. After undertaking basic development of the technology during the 1990s, GTC hung out a shingle, marketing itself as a technology platform for companies that either wanted to produce difficult-to-make pharmaceutical proteins or needed large quantities at low cost. The one catch was that regulators had never approved a transgenically produced drug, and the more than a dozen partners that GTC took on tended to view the technology as a backup in case other protein-drug development strategies did not work out. They were unwilling to accept the expense and risk of an arduous regulatory process for a pioneering form of drug manufacture.
GTC recognized the need to demonstrate on its own the potential for the technology and, in the late 1990s, began a clinical trial of human antithrombin for patients undergoing bypass surgery who develop resistance to the anticoagulant drug heparin. Transgenic antithrombin was intended to improve supply and address concerns about pathogens in the form of the drug isolated from human blood. The company completed the required clinical trials. But when the Food and Drug Administration asked for more data in late 2000—which would have necessitated additional testing—then chief executive Sandra Nusinoff Lehrman scrapped the effort. In mid-2001 Nusinoff Lehrman left, and her replacement, Geoffrey Cox, decided to proceed with development of transgenic antithrombin—this time in European clinical trials for patients with inherited antithrombin deficiency. Regulators there had recently issued guidelines that set out the requirements for getting approval for antithrombin.
The company still has a few partnerships. It also has a preliminary program to make other blood proteins, such as alpha-1 anti trypsin, and a clinical trial in the U.S. for ATryn. But its future hinges on the European approval. The company, which went public in 1993, has flirted with penny-stock status (less than $1 a share), and its cash levels are much depleted from what they were at the start of the decade. It has also experienced “restructurings,” layoffs that occurred in 2003 and 2004. “This is an important moment,” says Cox of the upcoming EMEA decision. “This isn’t a business for the faint of heart.”
Bioreactor Blues Other transgenic companies have also had a rough haul. The Scottish company PPL Therapeutics, which helped to clone Dolly, encountered difficulties and sold its remaining intellectual property to Pharming in 2004. The latter has staged a comeback since filing for protection from creditors in 2001. It hopes to get approval soon for a treatment for hereditary angioedema, a genetic disease that causes swelling from the absence of the C1 inhibitor protein.
If GTC survives, it could become the leader in transgenics. The impetus for starting the company still appears justified. The capital costs for a drug production facility using hamster cells can amount to $400 million to $500 million, Cox says, whereas a herd of goats can produce the comparable amount of drug for $50 million. “There’s still a need for alternative production methodologies,” says Philip Nadeau, who tracks GTC as an analyst with S. G. Cowen. “There are still proteins that are diffi cult to produce using traditional methods, and therefore a company like GTC should certainly have a niche.” ATryn’s uses could be broadened to encompass an array of treatments—for coronary bypass, burn or sepsis patients—that might, in total, bring in as much as $700 million annually, Cox estimates.
The drug appears to have surmounted an important technical hurdle: so far it has not created any adverse immune response in patients. But such events will always remain a worry. Researchers administering inhaled transgenic alpha-1 antitrypsin from sheep bred by PPL discovered that some patients suffered pulmonary symptoms that caused them to leave the trial—a possible immune reaction to residual proteins from the animal that remained after purification of the drug. The PPL drug, given on a longer term basis than ATryn is, needed to be better purified, notes Meade, GTC’s chief scientific officer.
Producing drugs in goats has so far elicited less criticism than the debate over genetically modified plants. Goats cannot drift with the wind like corn pollen, spreading their transgenes to unexpected places. “If it’s able to make drugs available that are not otherwise available by other methods and if it would make drugs cheaper, it would be certainly advantageous to consumers,” notes Jane Rissler of the Union of Concerned Scientists. “Frankly, consumers have not benefited very much [so far] from biotechnology in the agricultural sector.”
At GTC, the scrapie-free goats brought in from New Zealand are penned within a 190-acre enclosure on a 300-acre plot in Charlton, Mass. The animals are fed—and not permitted to graze—to diminish the possibility of contracting disease from contaminants in other animals. Thirty goats are devoted to making ATryn among a transgenic herd of more than 300, and an additional 1,200 nontransgenic animals are kept for breeding. “We have more veterinarians than M.D.s,” Cox says. If ATryn finally receives approval, traditional dairy farmers flirting with insolvency may gaze in astonishment at a product made in milk that commands thousands of dollars per gallon.