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FDA, Alexion Pharmaceuticals Reach Agreement on Protocols for Phase 3 Pexelizumab Trials

CHESHIRE, Conn., June 14 /PRNewswire-FirstCall/ -- Alexion Pharmaceuticals, Inc. announced today that they and their collaboration partner for pexelizumab, Procter & Gamble Pharmaceuticals, Inc. (P&GP), have received written confirmation from the U.S. Food and Drug Administration (FDA) indicating agreement with the protocols for two independent pivotal Phase III trials of the investigational drug pexelizumab. One Phase III protocol covers patients undergoing coronary artery bypass graft ("CABG") surgery and the second covers a separate program in patients experiencing acute myocardial infarction (AMI) treated with primary percutaneous intervention (PCI). The agreements for the two Phase III protocols for the separate clinical indications were reached under the FDA's Special Protocol Assessment (SPA) process, a procedure by which the FDA provides official evaluation and guidance on proposed protocols for pivotal Phase III clinical trials. It is expected that, if successful, each trial will complete the filing package that will serve as the primary basis of review for the approval of Biologics License Applications for each of these indications.

The first pivotal Phase III trial, called PRIMO-CABG-2, will examine the effects of pexelizumab on the composite endpoint of death or myocardial infarction at 30 days post procedure in moderate to high risk CABG surgery patients with or without concomitant valve surgery during cardiopulmonary bypass. The study is expected to enroll approximately 4,000 patients in the US and Europe. Alexion and P&GP are preparing to initiate the study in the near term.

The PRIMO-CABG-2 trial will mark the second pivotal Phase III study performed with pexelizumab in CABG surgery patients. Results of the first trial, known as PRIMO-CABG, were recently reported in the May 19, 2004 issue of the Journal of the American Medical Association. In the first trial, the primary endpoint in the PRIMO-CABG trial was a composite of the incidence of death or myocardial infarction, measured at 30 days post-procedure, in the subpopulation of patients undergoing CABG without concomitant valve surgery. Analysis confirmed that pexelizumab treatment was associated with a reduction in the primary endpoint, although it was not achieved with statistical significance (p=0.069). Additionally, in the 2,000 patient moderate to high risk study population from PRIMO-CABG with more than one pre-specified risk factor, Death/MI at Day 30 was reduced with statistical significance from 16.3% with placebo to 11.7% with pexelizumab (relative reduction 28%, p=0.003). This PRIMO-CABG study population forms the basis for the PRIMO-CABG-2 study. Further, the pexelizumab regimen appeared to be well tolerated.

The second pivotal Phase III trial, called APEX-AMI, will examine the effects of pexelizumab on death at 90 days post procedure in patients undergoing percutaneous intervention for acute myocardial infarction. The study is expected to enroll approximately 8,500 patients in the U.S., Europe, Australia and New Zealand. Alexion and P&GP are preparing to initiate the study in the near term.

The APEX-AMI trial follows the previously completed large Phase II study called COMMA which examined the effects of pexelizumab in AMI patients treated with PCI. As reported last year in the journal Circulation (September 9, 2003), the primary analysis of the COMMA trial showed that treatment with a bolus of pexelizumab followed by an infusion continuing to 24 hours did not significantly reduce infarct size (the primary endpoint) but was associated with a significant 70% reduction in 90 day mortality (placebo 5.9% vs. pexelizumab bolus/infusion 1.8%, p=.014). Further, the pexelizumab regimen appeared to be well tolerated.

"We are very gratified that by working with the FDA through the SPA process, we and our collaboration partner for pexelizumab, P&GP, have been able to successfully define clear paths forward for pexelizumab in both CABG and AMI patients," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "We are confident that, if successful, the PRIMO-CABG-2 and APEX-AMI trials should provide a solid basis to support separate biological license applications for the CABG and AMI indications. What remains now is to focus on the efficient and timely execution of these large clinical trials."

If approved, pexelizumab would represent the first of a new class of anti-inflammatory therapeutics (terminal complement inhibitors) for patients undergoing CABG surgery and for patients undergoing PCI for acute myocardial infarction.

Source: Alexion Pharmaceuticals

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