An NDA and MAA will be filed during the fourth quarter.
AstraZeneca reports that the Phase III trial comparing its antiplatelet therapy, ticagrelor, to Plavix showed that the compound had greater efficacy in the primary endpoint of reducing cardiovascular events. The reduction in risk of cardiovascular events with ticagrelor occurred early, and this benefit increased over time compared to Plavix, according to AstraZeneca. The company says that the results confirm its plan to submit an NDA and MAA during the fourth quarter.
This study, called PLATO, confirmed the clinical safety profile of previous trials, which showed no difference in major bleeding compared to clopidogrel. When PLATO minor bleeding was added to the major bleeding results, ticagrelor showed an increase versus clopidogrel. There was also an increase in nonprocedural related bleeding with ticagrelor. Within the patient subgroups of gender, weight, and history of stroke, ticagrelor showed no increase in the incidence of major bleeding versus clopidogrel.
PLATO analyzed 66 subgroups (33 efficacy and 33 safety subgroups). Thirty of the 33 efficacy subgroups analyzed were consistent with the analysis of efficacy in the overall population, showing a benefit for ticagrelor over clopidogrel. Of the three remaining subgroups, one (patients with weight below the gender-specific median) showed an attenuated benefit for ticagrelor over clopidogrel. The other two subgroups (patients not taking a statin medication on the day of randomization and those at sites in North America) showed no treatment advantage for ticagrelor.
Of the 33 safety subgroups analyzed, 32 were consistent with the analysis of safety in the overall population, showing no statistically significant difference between ticagrelor and clopidogrel. The remaining subgroup (patients with a BMI > 30 kg/m2) had major bleeding more frequently with ticagrelor than with clopidogrel.
Given the large number of tests performed these differences may have been due to chance, AstraZeneca claims. The observed difference in results between patients in North America and those enrolled elsewhere raises questions of whether geographic differences between populations of patients or practice patterns influenced the effects of the randomized treatments, although no apparent explanations have been found to date.
PLATO was a head-to-head 18,624 patient outcome study of ticagrelor plus aspirin versus the active comparator, clopidogrel plus aspirin, and was designed to establish whether ticagrelor could achieve meaningful cardiovascular and safety endpoints in ACS patients.
Ticagrelor is a reversibly binding oral adenosine diphosphate (ADP) receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP. ADP receptor blockade inhibits the action of platelets in the blood, reducing recurrent thrombotic events.
