PRIMO-CABG II: Pexelizumab fails to reduce death or MI after cardiac surgery

March 17, 2006

Atlanta, GA - Updated data presented this week at the American College of Cardiology 2006 Scientific Sessions has confirmed that pexelizumab (Alexion Pharmaceuticals), a terminal complement inhibitor that inhibits complement-mediated tissue damage, failed to reduce the incidence of death or MI at 30 days in patients undergoing coronary artery bypass graft (CABG) surgery.

It was reported by heart wire in 2005 that the drug would not meet the primary end point of the Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery II (PRIMO-CABG II) trial. Lead investigator Dr Peter Smith (Duke University Medical Center, Durham, NC) presented the final data showing a statistically insignificant trend toward reduction with pexelizumab compared with placebo.

"In the individual study, the drug failed to meet the primary end point, which was death or MI," Smith told heart wire . "The problem is that it didn't reduce MI as it has done in previous trials, so the composite end point wasn't as good because of that.

PRIMO-CABG II: Clinical end points at 30 days

End point Placebo (n=2112) (%) Pexelizumab (n=2142) (%) Risk reduction (%) p
Death or MI 16.3 15.2 6.7 0.201
MI 13.3 12.6 5.3 0.311
Death 4.6 3.8 17.4 0.177

This is the second major study of pexelizumab in CABG patients that has failed to show a significant reduction in the primary end point. The first trial, PRIMO-CABG, which was published last year, showed similar results, with a nonsignificant trend toward a reduction in death/MI. In that trial, however, there was a significant reduction in death/MI in a subgroup of patients judged to be high risk. Because of those findings, the PRIMO-CABG II trial was conducted in patients with a higher surgical risk profile.

Because of these disappointing results from PRIMO-CABG and PRIMO-CABG II, the APEX AMI trial, evaluating pexelizumab in ST-elevation-MI patients treated with primary PCI, was recently stopped. The trial is continuing until its halfway point, when investigators intend to perform a prespecified utility analysis.

Smith said that while the findings of PRIMO-CABG II are negative, in a review of all cardiac-surgery patients that have been randomized with pexelizumab, including PRIMO-CABG as well as another smaller trial—an analysis involving more than 7000 patients—there is a reduction in mortality that is statistically significant. In addition, a pooled analysis of pexelizumab in more than 9000 patients (CABG or STEMI) showed a significant 24% reduction in mortality, he reported.

"Any drug that can prevent this many deaths, in heart surgery as well as percutaneous coronary intervention and acute MI, really deserves to be strongly considered," said Smith. "We don't have too many weapons to fight inflammation that occurs in heart surgery with bypass. Speaking as a heart surgeon, I think we really need something to help us here."


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