Clinical Trial Results. org Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention The APEX AMI Investigators Published in JAMA January 3, 2007 Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention

Clinical Trial Results. org APEX AMI Trial: Background Complement is known to be both activated and a potential mediator of inflammation following reperfusion / reperfusion injury.Complement is known to be both activated and a potential mediator of inflammation following reperfusion / reperfusion injury. The goal of this trial was to evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30 day mortality from STEMI.The goal of this trial was to evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30 day mortality from STEMI. Complement is known to be both activated and a potential mediator of inflammation following reperfusion / reperfusion injury.Complement is known to be both activated and a potential mediator of inflammation following reperfusion / reperfusion injury. The goal of this trial was to evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30 day mortality from STEMI.The goal of this trial was to evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30 day mortality from STEMI. Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org Pexelizumab 2mg/kg bolus mg/kg/hr for 24 hours n=2860Pexelizumab 2mg/kg bolus mg/kg/hr for 24 hours n=2860 APEX AMI Trial: Study Design  Primary Endpoint: All-cause mortality through 30 days.  Secondary Endpoint: Death at day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 or 90.  Primary Endpoint: All-cause mortality through 30 days.  Secondary Endpoint: Death at day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 or 90. Placebo 2 mg/kg bolus mg/kg/hr for 24 hours n=2885Placebo 2 mg/kg bolus mg/kg/hr for 24 hours n= patients > 18 yrs with acute MI within 6 hours of symptom onset; high-risk anterior lateral or inferior MI; planned primary PCI; or new left-bundle branch block excluding those with prior fibrinolytic therapy for treatment of the index MI; complement deficiency; pregnant; breast-feeding; isolated, low-risk, inferior wall MI Prospective. Double-Blind. Placebo-Controlled. Randomized. Mean follow-up 90 days. 23% female, mean age 61 years, mean follow-up 90 days patients > 18 yrs with acute MI within 6 hours of symptom onset; high-risk anterior lateral or inferior MI; planned primary PCI; or new left-bundle branch block excluding those with prior fibrinolytic therapy for treatment of the index MI; complement deficiency; pregnant; breast-feeding; isolated, low-risk, inferior wall MI Prospective. Double-Blind. Placebo-Controlled. Randomized. Mean follow-up 90 days. 23% female, mean age 61 years, mean follow-up 90 days. R 90 days follow-up Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org Characteristic Placebo (n=2885) Pexelizumab (n=2860) Age (yrs) Median (IQR) Median (IQR) ≥75 (%) ≥75 (%) 61 (52-71) 479 (16.6) 61 (51-71) 498 (17.4) Women, No (%) 634 (22.0) 691 (24.2) Weight, median (IQR), kg 80 (70-91) Heart rate, median (IQR), beats/min 75 (64-86) 75 (65-86) Systolic blood pressure, median (IQR), mm Hg 133 ( ) Killip class, No (%) I II II III III IV IV 2580 (89.6) 236 (8.2) 33 (1.2) 32 (1.1) 2548 (89.2) 253 (8.9) 31 (1.1) 26 (0.9) APEX AMI Trial: Baseline Characteristics Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org Characteristic Placebo (n=2885) Pexelizumab (n=2860) Infarct location, No (%) Inferior Inferior 1180 (40.9) 1167 (40.8) Clinical History, No (%) Prior MI Prior MI Prior CHF Prior CHF Prior stroke Prior stroke Prior CABG Prior CABG Prior PCI Prior PCI History of diabetes History of diabetes Current smoker Current smoker 354 (12.3) 103 (3.6) 99 (3.3) 68 (2.4) 284 (9.9) 467 (16.2) 1252 (43.6) 340 (11.9) 105 (3.7) 117 (4.1) 60 (2.1) 278 (9.7) 446 (15.6) 1226 (42.9) Creatinine Clearance, median (IQR), mL/min 82.7 ( ) 83.0 ( ) APEX AMI Trial: Baseline Characteristics (cont.) Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org There was no difference in the primary endpoint (mortality at 30 days) between placebo and pexelizumab (3.9% vs 4.1% respectively), ie, each experiencing a low mortality.There was no difference in the primary endpoint (mortality at 30 days) between placebo and pexelizumab (3.9% vs 4.1% respectively), ie, each experiencing a low mortality. % patients APEX AMI Trial: Primary Endpoint p = 0.78 Armstrong et al., JAMA Jan; 297(1): Primary endpoint of 30 day mortality

Clinical Trial Results. org APEX AMI Trial: Secondary Endpoint The 30 day composite endpoing of death, cardiogenic shock, or congestive heart failure was similar between treatment groups (9.2% for placebo vs. 9.0% for pexelizumab).The 30 day composite endpoing of death, cardiogenic shock, or congestive heart failure was similar between treatment groups (9.2% for placebo vs. 9.0% for pexelizumab). Secondary composite endpoint of death, cardiogenic shock, or heart failure at 30 days % Patients p = 0.81 PexelizumabPlacebo Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org APEX AMI Trial: Secondary Endpoint (cont.) The secondary endpoint of mortality at 90 days remained low and was similar between both treatment groups (4.5% for placebo vs. 4.9% for pexelizumab).The secondary endpoint of mortality at 90 days remained low and was similar between both treatment groups (4.5% for placebo vs. 4.9% for pexelizumab). Secondary endpoint of mortality at 90 days % Patients p = NS PexelizumabPlacebo Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org APEX AMI Trial: Secondary Endpoint (cont.) The secondary composite endpoint of death, shock, or heart failure at day 90 was similar between both treatment groups (10.2% for placebo vs. 10.2% for pexelizumab).The secondary composite endpoint of death, shock, or heart failure at day 90 was similar between both treatment groups (10.2% for placebo vs. 10.2% for pexelizumab). Secondary composite endpoint of death, shock, or heart failure at 90 days % Patients p = 0.91 PexelizumabPlacebo Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org APEX AMI Trial: Sepsis In spite of the theoretical possibility of more infection with a complement inhibitor, sepsis, while uncommon in both groups, tended to be less common in patients treated with pexelizumab than with placebo (0.56 % vs. 0.90%; respectively, p=0.13)In spite of the theoretical possibility of more infection with a complement inhibitor, sepsis, while uncommon in both groups, tended to be less common in patients treated with pexelizumab than with placebo (0.56 % vs. 0.90%; respectively, p=0.13) Sepsis among treatment groups % Patients p = 0.13 PexelizumabPlacebo Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org APEX AMI Trial: Summary Among patients with ST elevation MI undergoing primary PCI, treatment with pexelizumab was not associated with a difference in mortality at 30 days compared with placebo.Among patients with ST elevation MI undergoing primary PCI, treatment with pexelizumab was not associated with a difference in mortality at 30 days compared with placebo. Prior data from the COMMA study demonstrated a reduction in mortality at 6 months with pexelizumab compared with placebo in patients treated with primary PCI; however, the COMMA trial was designed specifically to address infarct size, not mortality at 30 days.Prior data from the COMMA study demonstrated a reduction in mortality at 6 months with pexelizumab compared with placebo in patients treated with primary PCI; however, the COMMA trial was designed specifically to address infarct size, not mortality at 30 days. Among patients with ST elevation MI undergoing primary PCI, treatment with pexelizumab was not associated with a difference in mortality at 30 days compared with placebo.Among patients with ST elevation MI undergoing primary PCI, treatment with pexelizumab was not associated with a difference in mortality at 30 days compared with placebo. Prior data from the COMMA study demonstrated a reduction in mortality at 6 months with pexelizumab compared with placebo in patients treated with primary PCI; however, the COMMA trial was designed specifically to address infarct size, not mortality at 30 days.Prior data from the COMMA study demonstrated a reduction in mortality at 6 months with pexelizumab compared with placebo in patients treated with primary PCI; however, the COMMA trial was designed specifically to address infarct size, not mortality at 30 days. Armstrong et al., JAMA Jan; 297(1):

Clinical Trial Results. org APEX AMI Trial: Summary (cont.) In addition to the present study, the PRIMO-CABG II trial also showed no significant benefit on death or MI with pexelizumab in the setting of bypass surgery.In addition to the present study, the PRIMO-CABG II trial also showed no significant benefit on death or MI with pexelizumab in the setting of bypass surgery. Performance of PCI and bypass surgery can cause reperfusion injury and increase inflammation, which this compound was designed to inhibit.Performance of PCI and bypass surgery can cause reperfusion injury and increase inflammation, which this compound was designed to inhibit. Limited success has been reported to date for therapies that target reperfusion injury, although other agents are currently being investigated.Limited success has been reported to date for therapies that target reperfusion injury, although other agents are currently being investigated. In addition to the present study, the PRIMO-CABG II trial also showed no significant benefit on death or MI with pexelizumab in the setting of bypass surgery.In addition to the present study, the PRIMO-CABG II trial also showed no significant benefit on death or MI with pexelizumab in the setting of bypass surgery. Performance of PCI and bypass surgery can cause reperfusion injury and increase inflammation, which this compound was designed to inhibit.Performance of PCI and bypass surgery can cause reperfusion injury and increase inflammation, which this compound was designed to inhibit. Limited success has been reported to date for therapies that target reperfusion injury, although other agents are currently being investigated.Limited success has been reported to date for therapies that target reperfusion injury, although other agents are currently being investigated. Armstrong et al., JAMA Jan; 297(1):