FDA CLEARS THROMBOLYTIC DRUG FOR PHASE II CLINICAL TRIAL.
This follows British Biotech's submission of an Investigational New Drug (IND) application on February 19 this year to conduct a Phase II clinical trial of the drug in acute myocardial infarction (AMI).
The Phase II trial will be conducted by the US-based Thrombolysis in Myocardial Infarction (TIMI) Study Group in suitable heart attack patients, initially at two hospitals in the United States. The aim of the trial will be to test the ability of BB-10153, given at doses between 1 and 5mg/kg, to lyse (dissolve) clots and restore blood flow in the coronary arteries of heart attack patients and to determine the safety of the treatment, especially with respect to bleeding. In this trial BB-10153 will be administered within six hours of the onset of clinical symptoms.
Dr Eugene Braunwald, chairman of the TIMI Study Group said: "We are very interested in learning in this Phase II trial whether BB-10153 can successfully lyse clots and provide an acceptable safety profile in terms of bleeding risk."
Dr Elliot Goldstein, CEO of British Biotech, said: "There is a clear need for safe and effective treatment of thrombotic diseases such as heart attack and stroke. BB-10153 has the potential to meet this need. We are very pleased that the TIMI Study Group will be carrying out the Phase II evaluation of BB-10153 and look forward to working closely with the group and to receiving the benefit of their outstanding experience in this area."
The preclinical and Phase I testing of BB-10153 showed that the drug may overcome the risk of bleeding associated with currently-prescribed thrombolytic drugs. This is because BB-10153 is activated by thrombin, which is only produced at the site of a fresh blood clot. Therefore BB-10153, once activated, only dissolves recently-formed or still-forming clots.
The Phase I trial of BB-10153 in healthy volunteers was completed in 1999 and showed the drug to be safe and well tolerated. British Biotech has subsequently been working closely with DSM Biologics of Montreal, Canada, on the technology transfer and scale-up of manufacturing for the drug. DSM has now completed production of material to Good Manufacturing Practice (GMP) standards for the Phase II trial.
1. The TIMI Study Group
The Thrombolysis in Myocardial Infarction (TIMI) Study Group is an investigative team that has been at the forefront of clinical research in acute coronary syndromes over the past two decades. The TIMI Study Group organized in 1984 and led by Dr. Eugene Braunwald of Brigham and Women's Hospital in Boston, Mass., is committed to advancing the knowledge and care of patients suffering from acute coronary syndromes by performing clinical research.
BB-10153 is an engineered form of human plasminogen, modified so that it is activated to plasmin by thrombin, rather than by the body's natural plasminogen activators such as tpA. Thrombin-activatable plasminogen thus marks a new approach to thrombolysis in which thrombin, the key enzyme in blood clot formation, is utilised to initiate clot destruction.
Conversion of natural plasminogen to plasmin (the active fibrinolytic enzyme) occurs on cleavage by a specific plasminogen activator. Enzymes involved in blood clot formation cannot activate natural plasminogen. Thus, the coagulation cascade and the fibrinolytic systems are functionally separate. However, thrombin-activatable plasminogen such as BB-10153 circumvents the physiological haemostatic mechanisms and selectively induces lysis of newly forming thrombi.
BB-10153's extended half-life (three to four hours) enables it to persist in the blood as an inactive pro-drug, activated only at fresh or forming blood clots by the thrombin that is localized there. Therefore, in addition to lysis of an existing clot, BB-10153 may prevent reocclusion and reduce the need for administration of a separate antithrombotic agent.
In preclinical thrombolytic studies, the selective activation of BB-10153 at fresh clots resulted in highly localized plasmin activity. The preclinical data from these studies showed no evidence of systemic plasmin activity, no consumption of coagulation factors and no effect on bleeding time. BB-10153 may therefore cause fewer bleeding problems than current thrombolytics which, in contrast, do produce systemic plasmin at therapeutic doses. Furthermore, in the Phase I study of BB-10153, evidence of proof-of-concept fibrinolytic activity was obtained in ex vivo clot lysis assays and in vivo production of fibrin degradation products.
British Biotech specializes in the research, development and commercialization of new drugs to fight cancer and other diseases with limited treatment options.
The company currently has four products in active clinical development:
-- BB-10901: currently in Phase I/II in small cell lung cancer. British Biotech was granted exclusive European and Japanese development and commercialization rights in May 2000 under an agreement with ImmunoGen Inc. (Boston, USA); -- E21R: currently in Phase II in acute myeloid leukaemia. British Biotech was granted exclusive worldwide development and commercialization rights in December 2000 under an agreement with BresaGen Ltd (Adelaide, Australia); -- MG98: currently in Phase II trials in various cancers. British Biotech was granted exclusive European development and commercialization rights in February 2002 under an agreement with MethylGene Inc. (Montreal, Canada); and -- BB-10153: now entering Phase II studies in heart attack patients.
In research, British Biotech has two ongoing programs and access to a third a follows:
-- an Antibiotic Program based on peptide deformylase inhibitors (PDFIs). The objective is to start the clinical program in patients with serious chest infections in 2002; -- a research collaboration with Serono SA (Geneva, Switzerland) to identify new treatments for serious inflammatory diseases, particularly multiple sclerosis; and -- an exclusive option to take up European development and commercialization rights over MethylGene's cancer research program in small molecule inhibitors of DNA methyltransferase.
British Biotech also has collaborations with Schering-Plough Corporation, OSI Pharmaceuticals, Inc., DevCo Pharmaceuticals Ltd and Tanabe Seiyaku.
For more information, visit http://www.britishbiotech.com or call 212-696-5600.
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|Date:||May 1, 2002|
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