>>CHESHIRE, Conn., Nov. 18 /PRNewswire-FirstCall/ -- Alexion Pharmaceuticals Inc. (Nasdaq: ALXN - News) announced today that Dr. Christopher Granger, M.D., FACC, Associate Professor of Medicine, Director, Cardiac Care Unit of the Duke University Medical Center and Co-Director of Clinical Trials, Duke Clinical Research Institute, presented the preliminary results of two independent Phase II clinical trials, COMMA and COMPLY, evaluating the use of pexelizumab in acute myocardial infarction (AMI) patients. Alexion is developing pexelizumab together with Procter & Gamble Pharmaceuticals.
COMMA Trial: The first study, called the COMMA trial, evaluated the possible benefits of pexelizumab treatment in acute myocardial infarction patients who underwent primary percutaneous transluminal coronary angioplasty (PTCA). Results from COMMA, or "Complement Inhibition in Myocardial Infarction Treated with PTCA", showed that pexelizumab did not reach its primary endpoint of infarct size reduction as measured at 72 hours. However, pexelizumab administration was associated with a dose-dependent and statistically significant 70% reduction in 90 day mortality (placebo 5.9% vs. pexelizumab bolus/infusion 1.8%, p=.014), an important prospectively defined secondary endpoint.
Dr. Granger, who is Chairman of the COMMA and COMPLY Steering Committee, commented, "The COMMA results are very exciting because this is the only recent trial to find a mortality reduction with an adjunct to reperfusion therapy. The fact that mortality was reduced but that measured infarct size was not suggests that the effect may be through a completely novel mechanism of action. Inhibiting complement appears to prevent a variety of inflammatory pathways, including production of cytokines, programmed cell death, and nitric oxide, each of which could contribute to death following acute MI."
In COMMA, pexelizumab 2.0 mg/kg (n=262), pexelizumab 2.0 mg/kg followed by a 20 hour infusion at 0.05 mg/kg/hr (n=281), or placebo (n=271) was administered in a double-blind and randomized manner at 92 North American sites to 814 acute myocardial infarction patients who received angioplasty. Pexelizumab appeared to be well tolerated with the most common adverse events being chest pain, hypotension, nausea, and ventricular tachycardia. The mortality benefit with pexelizumab bolus/infusion observed at 90 days was maintained through 180 days. At 180 days, pexelizumab bolus/infusion was still associated with a significant 57% relative reduction in mortality compared to placebo administration (placebo 7.4% vs. pexelizumab bolus/infusion 3.2%, p=0.035). The incidence of cardiogenic shock was also lower with pexelizumab bolus/infusion (placebo 5.2% vs. pexelizumab bolus/infusion 2.8%, p=0.19) compared to placebo. As shown in the included survival analysis figure of the COMMA trial, pexelizumab administration was associated with an immediate, dose-dependent reduction in mortality that was sustained throughout the observation period (p=0.018 for the entire six month observation period). This significant reduction in mortality with pexelizumab was observed in the context of excellent overall care, with the concomitant treatment of approximately 90% - 95% of patients in each treatment arm with aspirin, coronary stents, IIb/IIIa antagonists, and beta blockers.
COMMA Trial: Dose-Dependent Reduction in Mortality graph available at: newscom.com
COMPLY Trial: The second study, called the COMPLY trial, evaluated the possible benefits of pexelizumab treatment in patients who sustained an AMI and were treated with a thrombolytic. COMPLY, or "Complement Inhibition in Myocardial Infarction Treated with Thrombolytics", which was conducted globally, did not reach its primary endpoint of infarct size reduction measured at 72 hours.
In COMPLY, pexelizumab 2.0 mg/kg (n=304), pexelizumab 2.0 mg/kg followed by a 20 hour infusion at 0.05 mg/kg/hr (n=309), or placebo (n=307) was administered in a double-blind and randomized manner at 87 North American sites, 22 Eastern European sites, and 10 South American sites to 920 acute myocardial infarction patients who received thrombolytics. Pexelizumab appeared to be well tolerated with the most common adverse events being headache, chest pain, hypotension, and ventricular tachycardia. The North American (n=434) population appeared to differ from the Eastern European (n=408) and South American (n=78) populations in several respects, both at baseline prior to drug administration and in terms of standard medical practice after hospital admission. Patients outside North America had greater cardiac damage at baseline and also lower utilization of revascularization procedures after study entry than did patients in North America.
There was no reduction in mortality at 90 days in the overall COMPLY population. However, a prespecified analysis of the pooled COMMA and North American COMPLY population (n=1248 in the total North American population) showed that, in this population, pexelizumab bolus/infusion was associated with a significant 55% reduction in 90 day mortality (placebo 6.3% vs. pexelizumab bolus/infusion 2.8%, p=.019). Separately, stroke, a complication of thrombolytic therapy, was reduced in the overall COMPLY population (placebo 2.6% vs. pexelizumab bolus/infusion 1.3%, p=0.26). Overall, in the combined COMMA and COMPLY population, pexelizumab appeared to be well-tolerated. The incidence of serious adverse events was similar in placebo (30%) and pexelizumab bolus (28%) and pexelizumab bolus/infusion (25%) treated patients.
"We are particularly encouraged by the apparently robust improvement in long-term mortality associated with pexelizumab administration demonstrated in the Phase II COMMA trial," stated Leonard Bell, M.D., Chief Executive Officer of Alexion Pharmaceuticals, Inc. "Certainly, in patients suffering life- threatening acute cardiovascular disorders, mortality remains the clinical gold standard. From a development point of view, the dose-dependent and sustained reduction in mortality observed in the COMMA trial with pexelizumab is consistent with the reduction in mortality observed with pexelizumab in the pooled COMMA and North American COMPLY population and with pexelizumab in the Phase IIb coronary artery bypass graft surgery trial reported at last year's AHA meetings. Together with our partner Procter & Gamble, we are planning to complete our analyses and then discuss these encouraging preliminary clinical results with the FDA so as to plan appropriate subsequent development of pexelizumab in patients suffering an acute myocardial infarction."
According to the 2002 Heart and Stroke Statistical Update from the American Heart Association, approximately 850,000 Americans are predicted to be admitted to a hospital with an AMI during the current year. From recent studies in patients with AMI (refs 1-3), it is expected that approximately 5- 10% of such patients would die within approximately 6 months of their index admission. Hence, approximately, 42,500-85,000 patients of these 850,000 patients would be expected to die from their acute myocardial infarction within this timeframe.<<
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Apparently, the good showing in mortality benefit somewhat make up for missing the primary EP: stock up almost to $13.
Edit: not even going to tell us about the numbers associated with primary endpoint.
Cheers, Tuck |
