Eli Lilly, Daiichi Sankyo's Effient misses primary endpoint in late-stage study

In Phase III study data presented at the European Society of Cardiology (ESC) Congress, Eli Lilly and Daiichi Sankyo announced that the oral antiplatelet therapy Effient (prasugrel) failed to meet the main goal of demonstrating superiority over Sanofi and Bristol-Myers Squibb's Plavix (clopidogrel) in certain patients with acute coronary syndrome (ACS) who were treated solely with medication. William Zoghbi, president of the American College of Cardiology, commented that "the outcome is a bit surprising because we think usually that more aggressive therapy in the face of ACS would lead to less adverse outcome."

The randomised TRILOGY ACS trial, which enrolled 9326 patients with unstable angina or non-ST elevation myocardial infarction who were to be medically managed without revascularisation, evaluated the safety and efficacy of Effient versus Plavix, both in combination with aspirin. The primary endpoint was the time to occurrence of the first instance of the composite endpoint of cardiovascular death, heart attack or stroke in patients under 75 years of age, the primary analysis population. Further, the sample size in the trial was selected to detect a 22-percent relative risk reduction in patients treated for up to 30 months with Effient compared with Plavix, the companies said.

The results, published in the NEJM, demonstrated that at 30 months cardiovascular deaths, heart attacks and strokes in the patient population occurred in 13.9 percent of patients on Effient versus 16.0 percent of those in the Plavix group, which the companies said did not represent a significant difference. However, with regard to adverse events, the data show there was also no significant difference in rates of thrombolysis in myocardial infarction (TIMI) major bleeding events, including life-threatening or fatal bleeds, with lead investigator Magnus Ohman saying "the safety here is very comforting."

Moreover, an analysis performed to account for multiple recurrent ischemic events suggested a lower risk among patients under 75 treated with Effient, while a post-hoc exploratory analysis observed a trend for a lower risk in heart attack, stroke and death among patients on Effient after 12 months of treatment, which Ohman said required further exploration. "The delayed treatment effect beyond 12 months observed in TRILOGY ACS had not been seen in earlier studies of shorter duration," Ohman noted. Elliott Antman, a spokesman for the American Heart Association, said the findings suggest more potent antiplatelet therapy probably have advantages for patients over time.

Effient was approved in the US in 2009 to reduce the risk of blood clots from forming in patients who undergo angioplasty. The antiplatelet agent was launched in Europe that same year, where it is sold as Efient, to prevent atherothrombotic events in patients with ACS undergoing percutaneous coronary intervention. The product recorded worldwide sales last year of $302.5 million, with analysts expecting sales to reach $1.1 billion by 2016.

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