Lilly Has The Last Laugh on Prasugrel

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  • 03/31/2008
Remember the media assault on Eli Lilly for suspending it's study of prasugrel last year, assuming malfeasance, substandard results, etc? Let's roll the tape from Matt Herper's dark commentary entitled "Lilly's Scary Silence":

"It's hard to see how that could be any comfort to investors. As is often true, there is a big downside risk to investors ahead of the data release on Nov. 4. But investors should be equally concerned about whether or not Lilly is giving straight answers about its data. If these studies do bode badly for prasugrel, investors have a right to know now. If they don't, Lilly still needs to give a clearer explanation. If the company can't do that, the safest thing is probably to assume the worst and sell the stock."

Science doesn't just snap to the whims of investors and reporters...but in case anyone cares here's an update from

Study Results Show Investigational Drug, Prasugrel, Cuts Risk of Stent-Related Clots by More than Half Versus Clopidogrel
March 29, 2008

Reductions seen as soon as three days and out to 450 days in patients who received either bare metal or drug-eluting stents
CHICAGO, March 29, 2008 /PRNewswire-FirstCall via COMTEX News Network/ -- The investigational antiplatelet drug prasugrel plus aspirin produced a marked and highly statistically significant reduction in the risk of coronary stent thrombosis (ST) - a major concern for physicians and patients with potentially fatal consequences - in patients who received a stent as compared to standard therapy with clopidogrel (Plavix®) plus aspirin (1.13 percent vs. 2.35 percent, p<0.0001), according to a stent analysis from the head-to-head TRITON-TIMI 38 trial.

The findings were presented today by Dr. Stephen Wiviott, an assistant professor of medicine at Harvard Medical School and investigator with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions with the American College of Cardiology's Innovation in Intervention: i2 Summit, in Chicago. In addition, the manuscript was simultaneously published online by the British medical journal, The Lancet.

In the TRITON-TIMI 38 trial, whose overall results were previously published, 12,844 of the 13,608 enrolled patients received at least one intracoronary stent. Of those patients, 6,461 received a bare metal stent (BMS), 5,743 patients received a drug-eluting stent (DES), and 640 patients received both BMS and DES at the time of enrollment. Stent thrombosis was a pre-defined secondary endpoint in the trial.

Prasugrel reduced the relative risk of coronary stent thrombosis (a new clot at the implanted stent site) over clopidogrel by 52 percent (1.13 percent vs. 2.35 percent, p<0.0001). In patients who received drug-eluting stents (DES), treatment with prasugrel reduced relative risk by 64 percent over clopidogrel (0.84 percent vs. 2.31 percent, p<0.0001), and by 48 percent in patients who received bare metal stents (BMS) (1.27 percent vs. 2.41 percent, p=0.0009).

In the analysis, prasugrel was consistent in reducing stent thrombosis, compared to clopidogrel, whether assessment occurred early or late (<30 days and greater than or equal to 30 days, out to 450 days, the median duration of therapy), regardless of the type of stent used (bare metal or drug-eluting), and regardless of which academic research consortium (ARC) definition of stent thrombosis was used - definite/confirmed stent thrombosis, definite/confirmed plus probable stent thrombosis, and definite/confirmed plus probable plus possible stent thrombosis. Definite/probable stent thrombosis was reduced by 59 percent in prasugrel-treated patients within 30 days of stent placement (0.64 percent vs. 1.56 percent, p<0.0001), and by 40 percent after 30 days (out to 450 days, 0.49 percent vs. 0.82 percent, p=0.03).

"Stent thrombosis is very serious, given the high risk of mortality. In TRITON, among 210 patients with definite or probable stent thrombosis, 186 (89 percent) either died or experienced an MI as a result of the event," said Francis Plat, M.D., vice president, clinical development, Daiichi Sankyo Company, Limited. "We were excited by the results of this study and the possibility that prasugrel may someday provide an alternative treatment for ACS patients undergoing PCI and receiving coronary stents."

A 19 percent reduction in risk was observed with prasugrel compared with clopidogrel among all patients receiving a stent (9.7 percent vs. 11.9 percent, p=0.0001) in TRITON's primary endpoint of cardiovascular death, non- fatal heart attack, or non-fatal stroke. A 20 percent relative reduction favoring prasugrel was observed in the primary endpoint in patients who received only a bare metal stent (10.0 percent vs. 12.2 percent, p=0.003), and in patients who received only a drug-eluting stent, results showed an 18 percent relative reduction in the primary endpoint favoring prasugrel (9.0 percent vs. 11.1 percent, p=0.019). Fatal stent thrombosis occurred in 18 (0.28 percent) patients treated with prasugrel and 29 (0.46 percent) patients treated with clopidogrel (p=0.10). Of note, of the 210 patients with stent thrombosis, 89 percent either died or had a myocardial infarction associated with the event.

The rate of major bleeding was higher in all patients receiving a stent treated with prasugrel vs. clopidogrel (2.4 percent vs. 1.9 percent, p=0.06). Major bleeding in both DES and BMS prasugrel-treated groups when compared to clopidogrel-treated patients was 3 percent vs. 2 percent (p=0.34 DES) and 2 percent vs. 2 percent (p=0.09 BMS).

In addition to a reduction in the primary endpoint (CV death, non-fatal heart attack, or non-fatal stroke), a significantly lower rate of the composite endpoint of cardiovascular death, heart attack or urgent target vessel revascularization (UTVR) was observed with prasugrel vs. clopidogrel for both bare metal stents (10 percent vs. 12 percent, p=0.009) and for drug- eluting stents (9 percent vs. 11 percent, p=0.004). A significant reduction was also seen in heart attack alone (8 percent vs. 10 percent, p=0.003, BMS and 7 percent vs. 9 percent, p=.006, DES). In DES-implanted patients, regardless of those receiving only sirolimus-eluting or paclitaxel-eluting stents, there was a similar magnitude of event reduction with prasugrel compared to clopidogrel.

For the entire cohort, sub-acute stent thrombosis (24 hours to 30 days) was 0.36 percent in prasugrel-treated patients vs. 1.19 percent in clopidogrel-treated patients (p<0.0001). DES-implanted patients had lower rates of stent thrombosis compared to BMS-implanted patients, and prasugrel was shown to significantly reduce stent thrombosis in DES-implanted patients within the first three days compared to clopidogrel (0.14 percent vs. 0.63 percent, p=0.003) as well as for thromboses that occurred >30 days following the DES implantation (0.42 percent vs. 0.91 percent, p=0.04).

"The reduction in risk seen in patients in this analysis treated with prasugrel over patients treated with clopidogrel is encouraging for high-risk patients with acute coronary syndrome being managed with PCI," said J. Anthony Ware, M.D., Lilly vice president for cardiovascular/acute care.

Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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