BOSTON, Mass., July 16, 2009 — Data presented at the annual meeting of the International Society on Thrombosis and Haemostasis (ISTH) in Boston show that ATryn® (Antithrombin [Recombinant]) safely prevents peri-operative and peri-partum acute deep vein thrombosis (DVT) or other venous thromboembolic events in patients with hereditary antithrombin deficiency (HD AT). ATryn is not indicated for treatment of thromboembolic events in HD AT patients. Additionally, data validate dosing algorithms that, along with AT activity monitoring, allow physicians to normalize antithrombin levels during the high-risk situations of surgery and childbirth.
“ATryn provides physicians with a safe and effective new treatment option for restoring and maintaining antithrombin levels,” said study co-investigator Michael Paidas, M.D., associate professor and director, Yale Women and Children’s Center for Blood Disorders. “This is important because these patients have a very high risk of venous thromboembolism that can lead to serious and potentially life threatening complications.”
Antithrombin is a naturally occurring protein that helps regulate the blood clotting mechanism in the body. People with HD AT have reduced antithrombin activity, putting them at increased risk for venous thromboembolic events (VTE), including pulmonary embolism and DVT. These patients are at particular risk during surgery and childbirth procedures, when antithrombin levels are often low and need to be carefully managed.
“Data presented show that these validated, individualized dosing algorithms can be used in these different HD AT patient populations, which allows physicians to adjust antithrombin levels based on the fluctuating needs,” said Dr. Paidas.
ATryn was created to provide a safe and reliable supply of recombinant antithrombin. Approved by the U.S. Food and Drug Administration (FDA) in February 2009 for the prevention of peri-operative and peri-partum thromboembolic events in patients with HD AT, it is the only recombinant form of antithrombin available in the world. Prior to the availability of ATryn, HD AT patients undergoing surgery or giving birth requiring an antithrombin therapy received treatment derived from human plasma. ATryn is not formulated with human plasma proteins.
Efficacy and Safety Results (Abstract PP-WE-405; Presented July 15, 2009)
The first poster provided a pooled analysis of two Phase III studies (N=32) evaluating the efficacy and safety of ATryn in patients with HD AT undergoing surgery (11 patients) or childbirth procedures (21 patients). Patients were administered ATryn intravenously to maintain antithrombin activity within normal range (80% to 120%). The incidence of acute DVT or other venous thromboembolic events was assessed within seven days of treatment discontinuation. Safety was based on adverse events and laboratory evaluations.
One patient had an asymptomatic, acute DVT that was seen on duplex ultrasound. No other patients had a confirmed thromboembolism up to seven days after cessation of treatment with ATryn. Of note, one patient was diagnosed with DVT 10 days after cessation of ATryn treatment and one patient was diagnosed with pulmonary embolism 14 days after finishing ATryn treatment, which reflect the high risk of VTE in HD AT patients and the need for sufficient follow-up anticoagulation.
The first poster also included a safety analysis which involved 47 patients from three studies (including a pharmacokinetic study). Adverse events were reported in 72 percent of patients and reflect those typically anticipated during the peri-partum and peri-operative period. Fifteen percent of patients reported an adverse event that was thought to be possibly related to ATryn, but none of these led to withdrawal from the study. Significant hemorrhage was reported in three patients: two of these episodes were associated with excessive heparin levels at the time of hemorrhage. The most commonly reported adverse events were anemia, vomiting, and headache (each 10.6%).
Dosing Algorithm Results (Abstract PP-TH-414; Presented July 16, 2009)
The second poster described the development and validation of a dosing algorithm using these two Phase III studies to help physicians maintain optimal levels of antithrombin in HD AT patients during high-risk surgical and childbirth procedures.
The analysis of AT levels from the first Phase III study (N=14: 9 pregnant and 5 surgical patients) that used the same dosing algorithm for pregnant and surgical patients found that pregnant HD AT patients have a higher clearance and volume of distribution than surgical patients, which led to the development of a specific dosing algorithm for pregnant patients.
The second study (N=18: 12 pregnant and 6 surgical) used a dosing formula based on patient type (pregnant or surgical) and, in most patients, AT level normalization markedly improved. Overall, a median of only one (range 0-6) infusion rate adjustment per patient was needed during treatment of a median of 3.2 days (range 0.9 — 14).
These studies support the use of separate dosing algorithms for pregnant and surgical patients.
Developed and manufactured by GTC Biotherapeutics, Inc. (NASDAQ: GTCB), ATryn was created to provide a safe and reliable supply of recombinant antithrombin. ATryn is made by processing the human antithrombin protein from the milk of a select herd of transgenic goats.
The process for producing ATryn involves scientists inserting DNA for the human antithrombin protein into a single-celled goat embryo. This embryo is implanted into a surrogate doe. The resulting transgenic offspring are able to produce high levels of human antithrombin in their milk.
This protein is collected and purified from the milk to produce ATryn, which is administered to patients by intravenous infusion.
Purified recombinant antithrombin has the same amino acid sequence as antithrombin derived from human plasma. Antithrombin (Recombinant) and plasma-derived antithrombin both contain six cysteine residues forming three disulphide bridges and 3-4 linked carbohydrate moieties. The glycosylation profile of ATryn is different from plasma-derived antithrombin, which results in an increased heparin affinity. When assayed in the presence of excess of heparin the potency of the recombinant product is not different from that of plasma-derived product.
Indications and Usage:
ATryn [Antithrombin (Recombinant)] is indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients. It is not indicated for treatment of thromboembolic events in hereditary antithrombin deficient patients.
Important Safety Information:
ATryn is contraindicated in patients with known hypersensitivity to goat and goat milk proteins.
Allergic-type hypersensitivity reactions are possible. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these symptoms occur during administration, treatment must be discontinued immediately.
The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when ATryn is added or withdrawn. To avoid excessive or insufficient anticoagulation, coagulation tests suitable for the anticoagulant used (e.g., aPTT and anti-Factor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours following the start or withdrawal of ATryn. Additionally, monitor the patients for the occurrence of bleeding or thrombosis in such situation.
The serious adverse reaction that has been reported in clinical studies is hemorrhage (intra-abdominal, hemarthrosis, and post procedural). The most common adverse events reported in clinical trials at a frequency of >5% are hemorrhage and infusion site reaction.
For more information, please see full Prescribing Information at www.lundbeckinc.com.
About Lundbeck Inc.
Lundbeck Inc. was established in March 2009 following the acquisition of Ovation Pharmaceuticals, Inc. by Lundbeck and has proven success in developing and commercializing high-need treatments. The company is committed to providing innovative therapies that fulfill unmet medical needs of people with CNS disorders and rare diseases for which few, if any, effective treatments are available. For more information, please visit www.lundbeckinc.com.
About H. Lundbeck A/S
H. Lundbeck A/S (LUN.CO, LUN DC, HLUKY) is an international pharmaceutical company highly committed to improve the quality of life for people suffering from central nervous system (CNS) disorders.
For this purpose Lundbeck is engaged in the research and development, production, marketing and sale of pharmaceuticals across the world, targeted at disorders like depression and anxiety, schizophrenia, insomnia, Huntington’s, Alzheimer’s and Parkinson’s diseases.
Lundbeck was founded in1915 by Hans Lundbeck in Copenhagen, Denmark, and employs today over 5.500 people worldwide. Lundbeck is one of the worlds leading pharmaceutical companies working with CNS disorders. In 2008, the company’s revenue was DKK 11.3 billion (approximately EUR 1.5 billion or USD 2.2 billion). For more information, please visit www.lundbeck.com.