Ticagrelor Achieves Greater Efficacy In Trial

AstraZeneca PLc (AZN) Tuesday announced results from the phase III head to head trial, PLATO – a study of platelet inhibition and patient outcomes – which demonstrate that ticagrelor (BrilintaTM) has achieved greater efficacy in the primary endpoint, reduction of cardiovascular events over clopidogrel (9.8% vs 11.7% at 12 months; 16% RRR; 95% CI, 0.77 to 0.92; p<0.001), without an increase in major bleeding (11.6% vs 11.2%, p=0.43). MAIN FACTS: -Efficacy endpoint driven by a statistically significant reduction in both CV death (4.0% vs 5.1%, p=0.001) and heart attacks (myocardial infarction, MI) (5.8% vs 6.9%, p=0.005) with no difference in stroke (1.5% vs 1.3%, p=0.22).

For patients in the PLATO study, the reduction in risk of cardiovascular events with ticagrelor occurred early and this benefit increased over time compared to clopidogrel. -Ticagrelor demonstrated a consistent positive effect across multiple secondary efficacy endpoints including CV death (and separately for all-cause mortality); myocardial infarction; the composite of myocardial infarction, stroke, and all-cause mortality. -Among patients who received a stent during the study, a 33% reduction in risk of definite stent thrombosis was achieved with ticagrelor. -Co looks forward to filing Brilinta with regulatory authorities in the fourth quarter. -The PLATO study confirmed the clinical safety profile of previous ticagrelor studies 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 (16.1% vs 14.6%, p=0.008). -There was also an increase in non-procedural related bleeding with ticagrelor. Within the patient subgroups of gender, weight, history of stroke/TIA, ticagrelor showed no increase in the incidence of major bleeding versus clopidogrel. -Consistent with phase II data, ventricular pauses (slowing of heart rhythms) occurred more often with ticagrelor but without associated symptoms or clinical consequences for the patient. -Dyspnoea was reported more frequently by patients on ticagrelor (13.8% vs 7.8%, p<0.001) but did not represent new or worsening heart failure or lung disease. Only one in 100 ticagrelor patients overall stopped taking study medication due to dyspnoea. -The PLATO results have confirmed AstraZeneca’s intention to submit the NDA and MAA with regulatory agencies during the fourth quarter of this year.