Industry Update: Acute Ischemic Stroke

First of all, I would like to thank the organizers of this meeting, particularly Dr. Michael Cowley, who asked me to attend. It’s an honor to be here. As a biochemist who has spent most of his life with his head in the “cell-culture” neighborhood, it is truly a privilege to address this group. Originally, Dr. Cowley asked me to review the trial of abciximab in acute ischemic stroke, but that was over two years ago. Preliminary data from the ABESTT pilot study (Abciximab in Emergent Stroke Treatment Trial), involving approximately 100 patients, showed some benefit. It was essentially a safety and dosing study. Centocor and Johnson & Johnson went on to pursue ABESTT II — a randomized, placebo-controlled trial, that includes 1,800 patients. At the IAGS meeting held in 2004, we talked about what Dr. Nick Hopkins had suggested, the blending of pharmacologic and interventional strategies in treating acute ischemic stroke. Given the limitations of neuro-interventional laboratories and trained interventionalists, it really makes sense, I think, to take the acute myocardial infarction (AMI) approach. That is, some kind of pharmacologic, reperfusion therapy delivered in the field to open the arteries up in a case of an ischemic situation, and then transfer the patient to an interventional facility. The AMI model is really the treatment strategy of choice now in coronary situations. Unfortunately, I’m here not to update the ABESTT II trial with positive news, but to tell you, in fact, that it was stopped about two months ago. The safety monitoring committee decided that the risk/benefit ratio was not acceptable. Close to 800 patients had been enrolled, almost halfway to the goal of 1,800 patients. There was a 6-hour time window for treatment, and it included a wake-up population as a companion arm. Treatment for that population, in fact, was stopped even earlier. It is easy to see that the longer the stroke has occurred, the worse the outcome is. It doesn’t appear that aggressive antiplatelet therapy with the coronary doses of abciximab will be useful as a reperfusion strategy for ischemic stroke. Again, very aggressive antiplatelet therapy, with a bolus, followed by an infusion for 12 hours, does not appear to be beneficial. The database is scheduled to be locked in about mid-March, and the data on the 800 or so patients will be presented at the European Stroke Meeting in May. Thus, in spite of the fact that it doesn’t look like abciximab would be useful, Johnson & Johnson is committed to pursuing pharmacology for the treatment of stroke. There are still some small investigator-initiated studies going on with lower doses of abciximab in combination with lytic therapy, and we’ll see where that takes us. But I do think that some treatment approach that is based in pharmacologic reperfusion, followed by aggressive interventional procedures, will eventually be a winner in the area of stroke. Realistically, we’re talking about 2010, although taking this stumble into consideration, it could be longer.