GTC Anticipates Reaching U.S. Market In 2009 With Human Antithrombin ATryn

Company tells “The Pink Sheet” DAILY it will seek indications for larger patient populations than initial target of hereditary antithrombin deficiency.

GTC Biotherapeutics says its recombinant human antithrombin ATryn met statistical requirements for the primary endpoint in a Phase III trial -though the study is incomplete due to the need for one more patient - and it plans a BLA for mid-2008. The Framingham, Mass.-based biotech will seek six-month priority review and hopes to bring ATryn to the U.S. market in 2009.

ATryn's U.S. approval process is proceeding on a rolling, fast track basis, a method under which FDA permits the manufacturer to submit portions of the filing as they are ready. GTC submitted the preclinical and manufacturing pieces of the BLA and expects to file complete Phase III data mid-year. The drug has orphan status.

The Phase III study is testing ATryn in at least 31 subjects, including 14 who participated in a prior European trial. The study is designed to determine noninferiority compared with plasma-derived antithrombin products in reducing incidence of deep-vein thrombosis or other thromboembolisms in patients with hereditary antithrombin deficiency who are undergoing high-risk surgical or childbirth procedures.

Counting 14 subjects from a trial used to support European approval, GTC has enrolled 30 patients to date. None of the 16 new patients experienced clinically relevant DVTs or other thromboembolisms during the observation period, the company says, meaning the trial already has reached the primary endpoint even though it is not fully enrolled. Enrollment has been extended through February to reach the 31-patient minimum.

ATryn received marketing authorization in Europe in August 2006 (¹ (Also see "Transgenic Goat Antithrombin Gains EU Nod" - Pink Sheet, 2 Aug, 2006.)). GTC's commercialization partner in Europe, Canada and the Middle East, Denmark's Leo Pharma, launched ATryn in the United Kingdom during the fourth quarter of 2007.

Leo now is establishing pricing in other European countries for the product, having done so already in Ireland and Greece. GTC also is seeking a U.S. partner for ATryn, the company told the "The Pink Sheet" DAILY.

"The real objective isn't so much for the partner to sell ATryn for the [hereditary deficiency] indication in the U.S.," the company explained. "We're much more focused on developing ATryn further clinically for much larger markets."

GTC plans to test and develop the drug for acquired antithrombin (AT) deficiencies such as disseminated intravascular coagulation (DIC) associated with sepsis. "That's a very severe condition; half the people who get that condition die, and they die very quickly," GTC told the DAILY. "There's really very little treatment that actually works for them."

Leo currently is conducting a Phase II trial in Europe to test ATryn's efficacy as DIC therapy. GTC believes winning approval for that indication would bring the drug higher market value and greater market supply need.

The company says there are nine types of acquired AT deficiency for which ATryn could provide effective treatment. GTC is involved in ongoing U.S. partnership talks with several entities and plans to conclude an agreement with one of them this quarter.

"Our objective is to have the partner do the commercialization of ATryn in the U.S. for hereditary deficiency in parallel with whatever acquired deficiency they're most interested in," the company said. "They may wish to also do DIC in the U.S., or they may choose one of the other indications that ATryn has value for. That's really, from our perspective, what we're most interested in - furthering the product in much larger indications."

GTC holds a U.S. patent through 2021 for its production process, in which therapeutic proteins are extracted from the milk of transgenic mammals. ATryn is extracted from the milk of goats that have a transgene for human AT.

"Whether it's ATryn or the other products in our pipeline, we're really dealing with known therapeutic entities," the company explained. "What our real strategy is is to use the unique characteristics of our technology, which is to express either difficult-to-express proteins like antithrombin and/or to get to large volumes in a very cheap manner so that we expand markets for products that today are limited by some sort of supply constraints."

Before winning approval in Europe, GTC had to convince the European Medicines Agency's Committee on Healthcare and Medicinal Products to reverse a negative opinion it issued in February 2006, which stemmed from questions about ATryn's pivotal trial. Of the 14 patients in that trial, five were treated during surgery, the other nine during childbirth. CHMP had requested data based on at least 12 surgical patients (² (Also see "EMEA Reverses Negative Decision On GTC’s Transgenic Antithrombin ATryn" - Pink Sheet, 2 Jun, 2006.)).

CHMP reversed its decision in June 2006 after GTC presented supporting opinions from hematology experts. The agency then determined that childbirth patients present the same high risk of DVT and other thromboembolisms, making data from all 14 subjects relevant.

-Joseph Haas ([email protected])