Following discussions with the FDA, Alexion Pharmaceuticals Inc. and partner Procter & Gamble Pharmaceuticals Inc. said they will start a Phase III program on the investigational heart drug pexelizumab in two separate indications.
The agency issued written confirmation indicating agreement with protocols for two independent pivotal Phase III trials for patients undergoing coronary artery bypass graft (CABG) surgery and for patients experiencing acute myocardial infarction (AMI) treated with primary percutaneous intervention (PCI), said Leonard Bell, CEO of Cheshire, Conn.-based Alexion.
The trials were cleared under the agency's special protocol assessment process meaning, if successful, the trials would be the basis for their respective biologics license applications. Bell expects to seek regulatory approval in CABG during the second half 2005 and in AMI patients within the next two to three years.
He said both trials will start in the near term.
Clearance to run the pivotal trials is a significant milestone for Alexion, which is preparing another drug, eculizumab, for Phase III studies in paroxysmal nocturnal hemoglobinuria.
"This illustrates that we are at the very latter stage of drug development," Bell told BioWorld Today.
Pexelizumab is a C5 complement inhibitor discovered by Alexion.
The CABG trial (also called PRIMO-CABG-2) will evaluate 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 about 4,000 patients at 200 to 250 sites in the U.S. and Europe.
Data from PRIMO-CABG-2 are expected to be filed in conjunction with an earlier pivotal Phase III in CABG surgery patients.
In the earlier trial, the primary endpoint 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 statistically significant (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 percent with placebo to 11.7 percent with pexelizumab (relative reduction 28 percent, p=0.003). That study population formed the basis for the PRIMO-CABG-2 study, the company said. (See BioWorld Today, Nov. 11, 2003.)
Results from PRIMO-CABG were reported in the May 19, 2004, issue of the Journal of the American Medical Association.
Meanwhile, the company expects to enroll 8,500 patients from the U.S., Europe, Australia and New Zealand in the other Phase III trial, known as APEX-AMI. The trial is designed to examine the effects of pexelizumab on death at 90 days post-procedure in patients undergoing percutaneous intervention for acute myocardial infarction. Alexion and P&GP are preparing to initiate the study in the near term.
Primary analysis of an earlier Phase II (referred to as COMA) in AMI patients treated with PCI 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 percent reduction in 90-day mortality (placebo 5.9 percent vs. pexelizumab bolus/infusion 1.8 percent, p=0.014). Further, the pexelizumab regimen appeared to be well tolerated, the company said.
Bell said he expects the single Phase III to be sufficient for the regulatory application.
The deal between Alexion and P&GP, an affiliate of Procter & Gamble Co., of Cincinnati, to develop pexelizumab dates back to early 1999. Initially, the deal was valued at about $95 million, but has since been renegotiated, leaving Alexion more responsibility in the U.S. and more profit potential. (See BioWorld Today, Jan. 27, 1999, and Dec. 13, 2001.)
The companies will split the cost of clinical trials. The CABG trial likely will cost about $60 million to $70 million, while the AMI trial is expected to hit the $100 million to $120 million range.
Alexion's stock (NASDAQ:ALXN) Monday was up 2 cents Monday to close at $17.80.