AstraZeneca's Brilinta beats Plavix in reducing CV deaths and heart attacks

UK drug major AstraZeneca has announced results from the Phase III head to head trial, PLATO (A Study of Platelet Inhibition and Patient Outcomes), which demonstrate that its investigational drug Brilinta (ticagrelor) achieved greater efficacy in the primary endpoint, reduction of cardiovascular events (CV death, MI, stroke) over blockbuster antiplatelet agent clopidogrel (Plavix/Iscover, marketed by France's Sanofi-Aventis and US major Bristol-Myers Squibb) (9.8% versus 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)." primary results from the plato study were presented at the european society of cardiology congress in barcelona, spain, and simultaneously published in the new england journal of medicine.>

This efficacy endpoint was 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). Ticagrelor is the first investigational antiplatelet that has demonstrated a reduction in CV death versus clopidogrel in patients with acute coronary syndromes (ACS).

AstraZeneca gets a significant boost from the results, because Plavix was the second-highest selling drug in the world last year with turnover of $8.6 billion. The UK firm plans to file for approval of Brilinta in the fourth quarter and aims to begin selling it next year, said Gunnar Olsson, the company's head of cardiovascular therapy.

Analysts are forecasting that Brilinta could achieve annual sales of $750 million, although given the size of the market it could secure significantly more than that. AstraZeneca faces threats on up to 65% of its revenue between now and 2016 from generic rivals, so the progress of the company's pipeline is crucial, notes the UK's Daily Telegraph. Analysts at Morgan Stanley have said that Brilinta offers "the most significant near-term pipeline opportunity" for the company.

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.

'The goal of new antiplatelet therapies is to improve the efficacy for patients without increasing the associated risks of treatment such as bleeding. Ticagrelor achieved a significant reduction in CV mortality in ACS patients versus clopidogrel and importantly without an increase in major bleeding,' commented Lars Wallentin, co-chairman of the PLATO Executive Committee, Uppsala Clinical Research Center in Sweden.