The European Medicines Agency's (EMEA's) review process was the first regulatory examination of a transgenically produced therapeutic protein anywhere in the world, representing the first real sign that the many transgenic drugs in the biopharma pipeline can gain acceptance from regulators.
"Our company has taken a simple concept and turned it into a practical reality and now the setbacks and challenges were worth it," Thomas Newberry, a spokesperson from GTC Biotherapeutics, developers of the drug, told In-PharmaTechnologist.com.
The news is welcomed by the many biotech firms who were shaken by the EMEA's initial decision to reject the drug, having invested hundreds of millions of dollars in transgenic technology.
Be it recombinant proteins in milk, polyclonal antibodies in eggs or digestive enzymes in corn, the potential of transgenic animals and plants for the cheap and efficient production of biopharmaceuticals is huge and could reap sales of more than $12bn (€10bn) by 2012 according to market research firm Kalorama.
The cost of producing biopharmaceuticals in bacterial or mammalian cell culture bioreactor facilities or through cell lines is much higher than in transgenic technology and with expression levels of 2 to 10 grams of recombinant protein per litre of milk being readily achievable in transgenic livestock, as opposed to highly optimised cell cultures that can typically generate 0.2 to 1 grams per litre of culture medium, scale is also an important benefit of this new technology, according to the Kalorama report.
ATryn, the new drug that has just been given the nod, is an anti-clotting agent and has been cleared for use in surgery in people with a rare congenital disease, antithrombin deficiency.
Only one person in every 3,000 to 5,000 people suffer from the condition, making clinical studies hard to conduct and as a result, European regulators initially rejected the drug on the grounds that not enough surgical cases were brought before them - they got five out of the twelve requested - and the fact that results from patients treated in a compassionate use programme and at childbirth could not be accepted.
However, on appeal, a reconsideration of the evidence to include the nine cases of women given ATryn in childbirth led to an EMEA backflip.
"ATryn may be a specialised drug for a rare hereditary disease but getting approval of the first drug manufactured by an animal or plant is a real stepping stone," said Newberry.
"The decision clearly validates this new method as a viable way to express protiens and lower the capital required to produce large volumes of proteins."
On receiving the good news US-based GTC received its first $1m milestone payment from LEO Pharma who the biotech firm partnered with to its develop and market the drug in Europe, Canada, and the Middle East.
GTC is also due a $2m payment upon final marketing authorisation by the European Commission, expected in three months time.
Upon approval, ATryn will be the only available antithrombin product that is not derived from the human blood supply and will also be the first antithrombin product approved for use in all 25 countries of the EU.
At this stage, GTC is unsure when the product will hit the market: "We were surprised that the EMEA decision was turned around so quickly so it is now up to LEO to decide when they can launch the product," said Newberry.
GTC will be responsible for ATryn production and in addition to sales and marketing, LEO is responsible for additional clinical development of ATryn in Europe.
LEO has already begun development of Atryn as a potential treatment for another indication - disseminated intravascular coagulation (DIC) - an area of major unmet medical need, occurring in 220,000 severe sepsis cases in the EU each year, of which half are fatal.
LEO has now requested scientific advice from the EMEA as the basis for the first planned clinical studies in DIC.
Meanwhile, GTC is still looking for approval in the US and said it will use the results from both the completed study of hereditary deficient patients reviewed by the EMEA and GTC's ongoing pivotal phase III study to prepare a Biologics License Application (BLA) for the US Food and Drug Administration (FDA), which is planned for mid-2007.
In addition to the ATryn program, GTC has in development a recombinant human alpha-1 antitrypsin, a recombinant human albumin, a CD137 antibody to stimulate the immune system as a potential treatment for solid tumors, and a malaria vaccine.
Other firms active in the transgenic arena include Pharming, Hematech/Kirin Brewery and Avigenics.
Dutch company Pharming is developing a drug for hereditary angioedema that is expressed in the milk of rabbits; US firm Hematech, owned by Japan's Kirin Brewery is focusing on human antibody-producing cows that will be used for the development of large quantities of polyclonal antibodies, which could form the basis of drugs for viral or bacterial infections and autoimmune disorders; while US-based Avigenics is pursuing avian transgenesis for treatments in oncology, infectious disease and autoimmune disease.
As the "pharming" trend takes hold, the EMEA's landmark approval signals the beginning of a new era of drug treatments and potential big dollar revenues.