By Brady Huggett
Alexion Pharmaceuticals Inc.'s initial analysis and unanticipated results of its completed Phase IIb trials for pexelizumab in patients undergoing cardiac surgery with cardiopulmonary bypass has the company looking toward Phase III sometime this year.
Pexelizumab, an anti-inflammatory C5 inhibitor monoclonal antibody fragment, is being developed in collaboration with the Procter & Gamble Co., of Cincinnati, and was previously known as 5G1.1-SC.
"We think we are first on the mountain with an anti-inflammatory drug," Leonard Bell, president and CEO of Alexion, said in a conference call Tuesday. "We're extremely excited. We plan to initiate a pivotal Phase III this year designed to confirm safety and efficacy."
The trial enrolled a large patient base - 914 - at 62 medical centers in the United States, with the patients split into two groups: those undergoing coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB) and those undergoing CABG with concomitant valve surgery during CPB. About 90 percent of patients were in the CABG-only group. Patients were treated with placebo, pexelizumab bolus, or pexelizumab bolus followed by a 24-hour infusion of pexelizumab at 0.05 mg/kg/hr. Patients were followed for safety and efficacy for 30 days.
Preliminary results showed pexelizumab suppressed complement in CPB patients, with the bolus and bolus-plus-infusion regimens showing complete suppression for four and 24 hours, respectively, and that both regimens appear to be safe and well tolerated in CPB patients.
However, unexpected results from the trial may prove to be the most significant. Pexelizumab, administered as a bolus plus infusion, was associated with a capacity to reduce post- CABG myocardial infarctions, reducing non-Q-wave myocardial infarctions by 66 percent at 30 days. Also at 30 days, pexelizumab reduced the death rate from 1.9 percent in the placebo group to 0.4 percent. As compared to the placebo group, pexelizumab reduced the composite incidence of death or myocardial infarction by 41 percent at 30 days.
"Basically, a Phase II is exploratory to figure out where a drug may work," Bell told BioWorld Today. "While the endpoint wasn't met, the data are related to a clinically important variable. Also, these trials help set up a pivotal Phase III trial and this trial has been very instrumental to doing that. It will help us get an endpoint formulation for Phase III."
A full analysis of the data is expected to be completed in the spring and will make its way through the presentation and publication circuit, but the mentioned Phase III should not be far off.
"We expect to start [Phase III] this year," Bell said. "But we have to finish our analysis and discuss it with the FDA."
Alexion, of Cheshire, Conn., and Procter & Gamble also are conducting two large Phase II studies in acute myocardial infarction patients. Another Alexion product, 5G1.1, completed a Phase II trial for the treatment of rheumatoid arthritis, is in a Phase II trial for membranous nephritis, and is in Phase Ib pilot studies for psoriasis, dermatomyositis and pemphigoid.
News of the data drove Alexion's stock (NASDAQ:ALXN) up $14.25, or about 25 percent, to close at $71.375 Tuesday. Bell agreed with the climbing valuation of Alexion shares.
"Well, it's a complicated trial and it was received positively," he said. "The market is always right."