KENGREAL® (cangrelor) clinical trial data

Significant relative risk reduction in periprocedural thrombotic events with a proven safety profile1,2

KENGREAL is specifically designed as an adjunct to PCI.1,2 See how it performed vs clopidogrel in the phase III pivotal trial CHAMPION PHOENIX.

CHAMPION PHOENIX phase III trial efficacy results1

As an adjunct to PCI, KENGREAL significantly reduced the primary composite endpoint events of death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis at 48 hours vs clopidogrel in an all-comer PCI patient population.

CHAMPION PHOENIX study design2

CHAMPION PHOENIX was a randomized, double-blind, placebo-controlled, phase III trial in 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy. Patients received a bolus and infusion of cangrelor or a loading dose of 600 mg or 300 mg of clopidogrel.

CHAMPION PHOENIX primary composite endpoint—MACE (death, MI, IDR, stent thrombosis at 48 hours): KENGREAL vs clopidogrel in an all-comer PCI cohort*1,2

Event rate (%)Hours from randomizationLog-rank P value=0.006relative riskreduction87654321006121824303642485.9%4.7%Patients at risk*547254705233516252295159522551555223515252215151522051515217514752135147Clopidogrel:KENGREAL:

mITT=modified intention-to-treat.

*The mITT population is all randomized subjects who received at least one dose of study drug and underwent the index PCI procedure.

Stent thrombosis at 48 hours*2

Event rate (%)Hours from randomizationPatients at risk*Log-rank P value=0.01relative riskreduction2.01.51.00.50.00612182430364248547254705426539254215389541953885419538654185385541753855416538354145383Clopidogrel:KENGREAL:1.4%0.8%ClopidogrelKENGREAL®(cangrelor)

mITT=modified intention-to-treat.

*The mITT population is all randomized subjects who received at least one dose of study drug and underwent the index PCI procedure.

Primary endpoint and its component events at 48 hours*1,2

KENGREAL(N=5470)Clopidogrel (N=5469)KENGREAL vs Clopidogreln (%)n (%)OR (95% CI)P value257 (4.7)18 (0.3)202 (3.7)10 (0.2)27 (0.5)Primary Endpoint:Death/MI/IDR/STSTDeath18 (0.3)322 (5.9)0.78 (0.66, 0.93)0.005254 (4.6)14 (0.3)36 (0.7)MIIDR

mITT=modified intention-to-treat.

*The mITT population is all randomized subjects who received at least one dose of study drug and underwent the index PCI procedure.

†Based on logistic model adjusted for loading dose and baseline patient status for primary endpoint.

Note: If a subject had more than one event at 48 hours, then worst outcome counted (death>MI>IDR>ST).

Breakdown of primary composite endpoint at 48 hours according to patient subgroups*1,2

mITT=modified intention-to-treat.

*The mITT population is all randomized subjects who received at least one dose of study drug and underwent the index PCI procedure.

Note: The figure presents effects in various subgroups, most of which are baseline characteristics and most of which were prespecified (patient presentation and weight were not prespecified subgroups). The 95% confidence limits that are shown do not take into account how many comparisons were made, nor do they reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be overinterpreted.

Supplementary FDA-requested endpoint:
Outcomes at 48 hours*1

This analysis omitted 2 subcomponent events from the primary endpoint of lesser clinical significance:

  • Intraprocedural stent thrombosis (defined as a new or increasing thrombus within or adjacent to a deployed stent occurring during the index PCI procedure)
  • MI with <10-fold increase in CK-MB, or with <5-fold increase in CK-MB in the presence of new Q waves or new left bundle branch block (LBBB)

mITT=modified intention-to-treat.

*The mITT population is all randomized subjects who received at least one dose of study drug and underwent the index PCI procedure.

†SCAI MI: CK-MB ≥10X ULN, or CK-MB ≥5X ULN with new Q waves or new LBBB.

‡ARC-ST defined according to the ARC definition.

ARC=Academic Research Consortium; CK-MB=creatine kinase MB isoenzyme; MI=myocardial infarction;
SCAI=Society for Cardiovascular Angiography and Interventions; ST=stent thrombosis.

Note: If a subject had more than one event at 48 hours, then worst outcome counted (death>SCAI MI>IDR>ARC-ST).

Bleeding events in CHAMPION PHOENIX

  • Patients receiving KENGREAL had no statistically significant increase in either GUSTO-defined severe bleeding or need for transfusion2
  • In CHAMPION PHOENIX, bleeding events of all severities were more common with KENGREAL than with clopidogrel1

Clinical bleeding results1

KENGREAL (n=5529)*Clopidogrel (n=5527)*857 (15.5%)11 (0.2%)21 (0.4%)825 (14.9%)45 (0.8%)12 (0.2%)33 (0.6%)Any GUSTO bleedingBleeding scaleMinor602 (10.9%)6 (0.1%)14 (0.3%)582 (10.5%)17 (0.3%)6 (0.1%)11 (0.2%)Any TIMI bleedingMajorllSevere/life-threateningModerateMild§

*Safety population is randomized subjects who received at least one dose of study drug.

†lntracranial hemorrhage or bleeding resulting in substantial hemodynamic compromise requiring treatment.

‡Requiring blood transfusion but not resulting in hemodynamic compromise.

§All other bleeding not included in severe or moderate.

‖Any intracranial hemorrhage, or any overt bleeding associated with a reduction in hemoglobin of ≥5 g/dL (or when hemoglobin is not available, an absolute reduction in hematocrit ≥15%).

¶Any overt sign of bleeding (including observation by imaging techniques) that is associated with a reduction in hemoglobin of ≥3 g/dL and <5 g/dL (or, when hemoglobin is not available, an absolute reduction in hematocrit of ≥9% and <15%).

GUSTO=GIobal Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries;
TIMI=Thrombolysis in Myocardial Infarction.

Important Safety Information

KENGREAL® (cangrelor) for Injection is contraindicated in patients with significant active bleeding.

KENGREAL® is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to cangrelor or any component of the product.

Drugs that inhibit platelet P2Y12 function, including KENGREAL®, increase the risk of bleeding. In CHAMPION PHOENIX, bleeding events of all severities were more common with KENGREAL® than with clopidogrel. Bleeding complications with KENGREAL® were consistent across a variety of clinically important subgroups. Once KENGREAL® is discontinued, there is no antiplatelet effect after an hour.

The most common adverse reaction is bleeding.

Indication

KENGREAL® (cangrelor) for Injection is a P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

References: 1. KENGREAL® (cangrelor) Prescribing Information. 2016. 2. Bhatt DL, Stone GW, Mahaffey KW, et al; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-1313. 3. Stone GW, Généreux P, Harrington RA, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention: core laboratory analysis from 10,854 patients from the CHAMPION PHOENIX trial. Eur Heart J. 2018;39(46):4112-4121.