Biotech Values

[drbio45]

PRIMO-CABG published: Pexelizumab fails to significantly reduce death/MI in surgery patients

http://www.theheart.org/article/137597.do


Tue, 18 May 2004 21:30:00 Michael O'Riordan

Seattle, WA -The results of the largest prospective clinical trial investigating the use of the terminal complement inhibitor pexelizumab in CABG patients are now published in the May 19, 2004 issue of the Journal of the American Medical Association.1 The trial, led by Dr Edward D Verrier (University of Washington, Seattle), showed that while the drug trended toward reducing the combined incidence of death or MI in patients randomized to treatment, the results failed to achieve significance.



Dr Edward D Verrier


The study, known as Pexelizumab for Reduction in Infarction and Mortality in Coronary Artery Bypass Graft Surgery (PRIMO-CABG), was first presented at the 2003 American Heart Association Scientific Sessions in Orlando, FL and previously reported by heartwire.

The randomized, double-blind, placebo-controlled trial included 3099 patients undergoing CABG surgerywith and without concomitant valve surgeryenrolled at 205 centers in North America and Europe. On entry, patients were randomized to receive placebo or pexelizumab in a 2.0-mg/kg bolus or pexelizumab in a 2.0-mg/kg bolus followed by a 24-hour infusion of pexelizumab at 0.05 mg/kg per hour.

The primary analysis was a composite of the incidence of all-cause mortality or MI at 30 days in the CABG-only population (n=2746). Secondary analysis included the composite end point of death/MI in the CABG-only patients at day 4, death/MI in the overall intent-to-treat population (CABG patients with and without valve surgery) at day 4 and day 30, and death at 90 days.

In the CABG-only population, treatment with pexelizumab resulted in an 18% relative reduction in risk of death/MI at 30 days compared with placebo. Although this primary end point failed to achieve significance, investigators report that when the overall results in the intent-to-treat population were analyzeda prespecified secondary analysis that includes CABG patients with and without concomitant valve surgerytreatment with pexelizumab did result in a statistically significant 18% relative risk reduction compared with patients receiving placebo.


Primary end point of death/MI at 30 days in the CABG-only populations

Primary end point
Placebo (n=1368)
Pexelizumab (n=1378)
Risk reduction
p

Death/MI at 30 days (%)
11.8
9.8
18
0.07





Secondary end point of death/MI at 4 days in CABG-only population

Secondary end point
Placebo (n=1368)
Pexelizumab (n=1378)
Risk reduction
p

Death/MI at 4 days (%)
10.0
7.4
26
0.01





Treatment effect in the overall intent-to-treat population (CABG patients with and without concomitant valve surgery)

Secondary end points
Placebo (n=1546)
Pexelizumab (n=1553)
Risk reduction
p

Death/MI day 4 (%)
11.9
9.1
24
0.008

Death/MI day 30 (%)
14.0
11.5
18
0.03

MI day 4 (%)
11.1
8.4
24
0.01

MI day 30 (%)
12.0
9.8
18
0.042

Death at 90 days (%)
4.8
3.6
25
0.096


To download tables as slides, click on slide logo below

"Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction at 30 days after the procedure among all 3099 patients undergoing CABG with and without valve surgery," conclude Verrier and colleagues.

The investigators suggest the study was underpowered to detect the observed drug effect in the CABG-only subpopulation. The PRIMO-CABG trial prespecified that 353 patients who underwent valve surgery be excluded from the primary analysis because pexelizumab was not believed to have a treatment effect in these patients.

In a post hoc analysis, event-free survival remained significantly improved through day 180, suggesting a reduction in early perioperative MI with pexelizumab results in a sustained reduction in clinical morbidity and mortality, they report.

In a previous interview with heartwire, Verrier noted that 67% of patients enrolled in the study had more than one risk factor. In these patients, pexelizumab significantly reduced the combined incidence of death or MI by 28%. He said that these results are particularly impressive considering that high-risk patients are more representative of the type of patients surgeons are seeing on the operating table.