New Oral Anticoagulant and Cancer Drug Believed to Be Firsts
McCann, Jean, Drug Topics
Favorable clinical trial reports on three unusual drugs aroused considerable interest at the annual meeting of the American Society of Hematology held in New Orleans recently. Still investigational at present, they are:
*the first oral anticoagulant (H376/ 95, AstraZeneca) to be introduced in 50 years
*an oral inhibitor(ST1 571, Novartis) that knocks down the high white blood cell counts of patients with leukemia who are refractory to interferon therapy *the once-banned thalidomide, which has been making a successful comeback (Thalomid, Celgene Corp.). Some 25 reports at this meeting addressed its successful application in chronic myelogenous leukemia and other hematologic diseases. According to the manufacturer, a pivotal trial for thalidomide for multiple myeloma is being considered for approval by the Food & Drug Administration.
As for the new oral anticoagulant, it has several unique aspects. Its mechanism of action is different from that of all other anticoagulants in that it acts as a direct thrombin inhibitor only. Also, it is convenient as an oral drug. So indicated its lead investigator, Bengt Eriksson, M.D., who is associate professor of orthopaedic surgery at the Sahlgrenska University Hospital in Gothenburg, Sweden. However, he added, the drug also comes in an injectable formulation for times when a patient can't swallow a pill, such as just prior to surgery
Another advantage Eriksson sees is that patients on H376/95 do not require coagulation monitoring. The therapeutic window, he noted, is far wider than that for either heparin or warfarin. In addition, he found no interactions with food or with other drugs.
In safety and efficacy studies in 300 patients undergoing total hip or knee replacement, Eriksson found the side effects to be similar to those in patients receiving a low molecular weight heparin. The pooled incidence of proximal deep vein thrombosis was 3% for the prodrug and 7% for the low molecular weight heparin, dalteparin (Fragmin, Pharmacia & Upjohn).
Eriksson added that the number of people needing a drug like this to prevent deep vein thrombosis following orthopedic joint surgery is already about a million a year in the United States and Europe--and that number, with the aging of the population, is certain to increase, he said.
The aging of the population is also likely to create a rising demand for Novartis' new drug, which inhibits the tyrosine kinase of the Bcr/ABLfusion oncoprotein, created by chromosomal translocation--the exchange of chromosomes 9 and 22. …