Eli Lilly, Daiichi-Sankyo Announce Submission of Prasugrel NDA in U.S.

According to the two companies, the NDA was submitted on 26 December 2007, and if approved prasugrel will be marketed under the brand name Effient. The companies have applied for an initial indication to treat patients with acute coronary syndrome (ACS) who are managed with percutaneous coronary intervention (PCI), including coronary stenting.

The NDA was based on data from several clinical trials, including the large-scale TRITON-TIMI 38 trial. This evaluated the safety and efficacy of prasugrel, compared with Sanofi-Aventis's Plavix (clopidogrel), in reducing ischemic events such as non-fatal heart attack, non-fatal stroke and cardiovascular death in 13,608 patients. The TRITON study showed that treatment with prasugrel resulted in a 19% relative risk reduction compared with clopidogrel in all ACS patients in the primary composite endpoint of non-fatal heart attack, non-fatal stroke or cardiovascular death. Prasugrel also showed a 52% relative risk reduction compared with clopidogrel in stent thrombosis, and a 30% relative risk reduction compared to clopidogrel in a subset of patients with diabetes in relation to non-fatal heart attack, non-fatal stroke or cardiovascular death. Risk reductions in the primary composite endpoint with prasugrel compared to clopidogrel were seen after three days and continued to diverge for 15 months (the duration of the trial).

As has been documented in the past, the TRITON study also produced some less positive aspects for prasugrel, and in particular its connection with serious bleeding (see United States: 5 November 2007: Eli Lilly’s Prasugrel Proves Effective, But Bleed Risks Create Uncertainty).

The risk of non-coronary artery bypass grafting (non-CABG) bleeding in prasugrel-treated patients was 2.2%, compared to just 1.7% for patients treated with clopidogrel. Meanwhile, the rates of life-threatening bleeding amounted to 1.3% for prasugrel and 0.8% for clopidogrel. In terms of death from cardiovascular causes, there was a 2% risk for prasugrel-treated patients compared with a 2.2% risk for clopidogrel-treated patients. Finally, there was very little difference In terms of all-cause death, with the respective rates standing at 2.8% and 2.9%.

The overall results demonstrated that for every 1,000 patients treated with prasugrel as compared with clopidogrel, there were 22 fewer patients with heart attacks and five more non-CABG-related TIMI major bleeds.

Outlook and Implications

The imminent submission of an NDA for prasugrel was widely anticipated, following the publication of results from the Phase III TRITON trial. In the event, the submission was only slightly delayed, despite prasugrel's relatively high risk for causing serious bleeding (see United States: 3 January 2008: Lilly Plans Imminent NDA Submission for Prasugrel).

If the NDA is viewed favourably, Effient will be in a position to challenge Plavix. However, the small difference in terms of all-cause death means that Effient will face a tough battle to replace Plavix as the industry-standard drug. Furthermore, Effient must make its mark sooner rather than later, given that generic versions of clopidogrel are likely to appear from 2011.

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