Rightfully so, strokes are scary. Around 140,000 French people are victims of it each year, and they are now considered in Europe as the leading cause of death ahead of breast cancer in women. The most common form, ischemic stroke (80% of cases), results from the formation of a clot in the cerebral arteries. By suddenly interrupting blood flow to the brain, it causes the targeted death of neurons, which when the patient survives can irreversibly alter cognitive abilities related to speech, vision, movements or even balance. A handicap which affects half of the patients treated.
“The problem is that there is currently only one treatment for acute ischemic stroke. And because its effectiveness remains limited, it is urgent to find new therapeutic solutions,” underlines Professor Charlotte Cordonnier, head of the vascular neurology department at Lille University Hospital. In this crazy race for treatments, glenzocimab has just won another victory. Initially developed by a French researcher, this candidate treatment was the subject of phase 1 clinical trials in healthy volunteers in 2019. Then scientists tested it in patients as part of phase 1b clinical trials. /2. Although they still remain very preliminary, the results published in The Lancet Neurology provide the first evidence of its effectiveness in patients.
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To date, the treatment of ischemic stroke consists of dissolving the clot in question via the injection, intravenously, of a medication which thins the blood. We are talking about thrombolysis. But when a large vessel is affected, this solution is often not sufficient. In 70 to 80% of cases, additional intervention by thrombectomy is necessary to extract the residual clot, resistant to thrombolysis. And despite these treatments, 54% of patients have significant after-effects. “One of the most problematic aspects remains that thrombolysis promotes bleeding, thus increasing the risk of disability,” raises Professor Cordonnier.
By directly attacking the blood cells that aggregate, glenzocimab opens up new treatment perspectives that would make it possible to overcome this constraint. This monoclonal antibody developed by the start-up Acticor Biotech targets a protein, glycoprotein VI (GPVI), involved in the formation of clots which is only expressed on the surface of one type of blood cell, platelets. “By attaching specifically to the surface of platelets, it prevents them from aggregating on the mass already formed and thus minimizes the risk of obstruction,” describes Professor Mikaël Mazighi, neurologist at Lariboisière hospital, who led the ‘study.
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In this new study, 160 patients from 6 countries (France, Spain, Belgium, Germany, Switzerland and Italy) received glenzocimab in addition to the standard treatment (thrombolysis associated or not with thrombectomy). The objective was to evaluate its good tolerance and to ensure that its administration is not accompanied by an increased risk of bleeding. An objective which has largely been achieved. “Its effect on the number of deaths even exceeded expectations,” adds Professor Mazighi. Indeed, the mortality rate of patients who received glenzocimab was reduced by half compared to the placebo group (which only received the reference treatment), going from 19% to only 8%. This is the first clinical study to demonstrate a significant reduction in the mortality of patients suffering from ischemic stroke.
This reduction in the number of deaths was linked to the considerable reduction in the rate of intracranial hemorrhages, lowered to 1.8% for treated patients compared to 7.8% in the placebo group. “These results are very encouraging, because they show that glenzocimab, administered in combination with reperfusion treatments, could not only reduce mortality but also the risk of potentially serious bleeding,” comments Professor Cordonnier. However, before considering its marketing, other trials including more patients, with longer follow-up, are necessary.
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To date, two phase 3 trials are underway. One, the ACTISAVE trial, was conducted internationally in 400 patients and should be published next spring. The other, the GREEN trial, is still in progress. Carried out in a French cohort, it aims more specifically to test the effectiveness of glenzocimab on the autonomy at three months of the most severe cases of ischemic stroke, that is to say those which required a emergency treatment by thrombectomy. If this evidence of effectiveness were to consolidate, it would take at least five years to see glenzocimab added to the therapeutic arsenal for ischemic stroke, scientists estimate. “Since every minute counts, the craziest objective would be to be able to use it from the ambulance,” underlines Professor Mazighi. But one thing at a time. At the moment we still have to go through the development stages.”
