Mr. Collen, a researcher who was involved in the early developmentof tissue plasminogen activator (t-PA), Genentech Inc.'s blockbusterclot-busting drug, is now conducting Phase I/II clinical trials withstaphylokinase (STA), a protein that may prove as effective and lessexpensive than t-PA in dissolving blood clots that block blood flow tothe heart.Staphylokinase is a protein secreted by certain strains ofstaphylococcus aureus bacteria. STA is able to activate plasminogen inthe blood of some animals. Plasminogen in turn forms plasmin, anenzyme that digests the protein fibrin, which is the primary componentof blood clots.Researchers who have studied STA in animal models using dogs,found that STA proved disappointing as a thrombolytic. However,Collen, Marc Verstraete, and their colleagues at the KatholiekeUniversiteit in Leuven, Belgium, decided that STA deserved re-evaluation. In experiments with rabbits, hamsters and a few baboons,they found that STA proved as effective as t-PA in dissolving bloodclots.In 1992, Collen and his colleagues began a Phase I/II clinical trial inhumans. Collen presented preliminary results from the study, in which100 subjects are to be enrolled, at the fourth annual Bristol-MyersSquibb Cardiovascular Research Colloquium at Rockefeller Universityheld recently in New York.The colloquium was held in conjunction with the presentation to Collenand Verstraete of the Bristol-Myers Squibb Award for DistinguishedAchievement in Cardiovascular Research. However, Collen andVerstraete are not associated with Bristol-Myers Squibb and the STAtrials are being conducted under the auspices of KatholiekeUniversiteit's internal review board.The results presented were from a preliminary study of 35 patients withmyocardial infarction who were given therapeutic doses of STA. Theefficacy of STA in 25 of these patients was compared with the efficacyof t-PA in another group in a randomized trial. Both groups alsoreceived heparin, an anticoagulant, and aspirin, which inhibits plateletaggregation."The efficacy of STA was found to be comparable with that of t-PA. Itappears to have more efficacy than streptokinase, anotherthrombolytic," Collen told BioWorld. "These are very preliminaryresults, but STA looks very promising."Because humans generally don't have antibodies against STA, allergicreactions could be less frequent than with streptokinase, Collen said.He noted that STA might also produce fewer side effects, such asbleeding, than t-PA, which has to be administered in high, potentiallytoxic doses in order to be effective.Collen said STA could also have a substantial cost advantage over t-PA. "I don't know how much of the price of a drug is determined byproduction costs and how much by development costs. However, interms of real production costs, STA would be cheaper than t-PA. STAis a simple protein and it would be easier to make," Collen said.Although the Phase I/II study is not yet complete, Collen said his groupis already gearing up for a Phase II trial. An organization is beingformed to conduct a large-scale clinical trial in collaboration with acorporate partner, Medac, of Hamburg, Germany. A small pilot trial isalso to be done in 10 patients to study efficacy and dosage.
-- By Philippa Maister
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