Repligen Corp.'s recombinant platelet factor 4 (rPF4) appears tobe a safe therapy for reversing the anti-coagulant effects ofheparin during cardiac catheterization.
Results of the Phase I trial on rPF4 were presented Wednesdayat the annual meeting of the American Heart Association inAtlanta.
The anti-coagulant heparin is used in essentially every openheart operation and a good portion of the diagnostic cardiaccatheterization procedures performed annually in the U.S.
Once the procedure is complete, physicians usually neutralizethe heparin with protamine (although heparin wears off byitself in about four hours). But protamine produces side effectsthat are both unpredictable and can be quite serious or evenfatal.
The open-label trial on rPF4, which began in April, included atotal of 18 patients. The study was divided into two phases,explained Gregory Dehmer, principal investigator for the studyand director of the C.V. Richardson Cardiac CatheterizationLaboratory at the University of North Carolina.
The first phase of the trial involved a total of 12 patients, threeper dose group. The study was performed in a cardiaccatheterization lab where the drug could be administered andits effects monitored under highly controlled conditions.
The patients received 0.5, 1.0, 2.5 or 5.0 milligrams rPF4 perkilogram of body weight intravenously over one- to three-minute time frames. According to Dehmer, all doses wereeffective in reversing the anti-coagulant effects of heparin(5,000 units).
In the second phase of the trial, six more patients were dosedwith rPF4, at 1 milligram per kilogram, in "a situation moretypical of what they might experience in the clinic," saidDehmer. Again, the drug was "highly effective and completelyneutralized the anti-coagulant effect of heparin in five of thesix patients" and in the sixth rPF4 appeared to be effective, headded.
"Based on these data, we feel we have a very safe profile atdoses that are five times higher than those that wouldprobably be used in the clinic," said Dehmer.
Dehmer will be the lead clinical investigator on the Phase IItrials of rPF4 in cardiac catheterization, which will be ready togo as soon as FDA gives the nod, explained Clare Clifford,director of corporate communications at Repligen of Cambridge,Mass. The company also plans to test rPF4 in coronary arterybypass graft surgery. Both trials should be under way by thefirst quarter of next year, Clifford said.
Repligen's stock gained 25 cents a share on Wednesday, closingat $9.25.
-- Jennifer Van Brunt Senior Editor
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