Effient is approved by the FDA

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Daiichi Sankyo and Eli Lilly have announced that the FDA approved Effient (prasugrel) tablets for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes who are managed with percutaneous coronary intervention (PCI).

Effient helps keep blood platelets from sticking together to form clots. Taking Effient with aspirin after PCI has been shown to reduce the chances of having a cardiac event and stent thrombosis among patients with acute coronary syndromes (ACS).


Effient should be initiated with a loading dose of 60mg followed by a maintenance dose of 10mg once daily. In addition, for those patients who weigh less than 132 pounds (60kg), physicians should consider lowering the maintenance dose to 5mg once daily. Patients taking Effient should also take 75mg to 325mg aspirin orally once daily, according to their doctors’ instructions.


“The data from the TRITON-TIMI 38 phase III pivotal trial provide compelling evidence that treatment with prasugrel significantly reduced the combined risk of cardiovascular death, heart attack or stroke over the current standard of care, clopidogrel, across a wide variety of patient types,” said lead TRITON-TIMI 38 investigator Elliott Antman, professor of Medicine at Brigham and Women’s Hospital (BWH) in Boston and senior investigator with the BWH TIMI Study Group. “Prasugrel is an important new option for patients with ACS who are managed with PCI. Prasugrel was associated with a significantly higher risk of serious bleeding events compared with clopidogrel. However, appropriate patient selection may help reduce this risk.”


The risk of bleeding was highest in Effient-treated patients who were either 75 years of age or older, weighed less than 132 pounds (60kg), or who had a prior history of transient ischaemic attacks (TIA) or stroke. Effient is contraindicated in patients with a history of prior TIA/stroke. It is generally not recommended in patients 75 years of age or older, except for patients in high-risk situations, such as those with diabetes or a history of prior heart attack.


Daiichi Sankyo and Eli Lilly co-developed Effient, which was discovered by Daiichi Sankyo and its Japanese research partner, Ube Industries.


TRITON-TIMI 38 trial
The approval was based on results from the pivotal phase III TRITON-TIMI 38 clinical trial, which compared Effient with Plavix (clopidogrel bisulphate, Sanofi-aventis) in reducing cardiovascular events in 13,608 acute coronary patients managed with PCI. The study showed that Effient taken with aspirin had a 19% relative risk reduction of the combined endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke versus Plavix taken with aspirin. This benefit was driven predominantly by reduction in heart attacks. The benefit of Effient compared with Plavix was seen as early as three days and continued over the 15 months of the trial. In addition, there were fewer stent-related clots (known as stent thrombosis) in patients treated with Effient compared with Plavix (a relative risk reduction of approximately 50%).


The risk of non-coronary artery bypass graft related bleeding, which included life-threatening and fatal bleeding, was significantly higher with Effient (2.2%) compared with Plavix (1.7%). When compared with the overall treatment population, the risk of major bleeding was highest among those patients treated with Effient who were either 75 years or older, had a body weight less than 132 pounds, or had a prior history of transient ischaemic attack/stroke.


An analysis from TRITON-TIMI 38, weighing the risk of major bleeding and the reduction in cardiovascular events, found an overall benefit significantly favouring Effient compared with Plavix. For every 1,000 patients treated with Effient as compared with Plavix, there were 23 fewer patients with heart attacks and six more with major bleeding events.


In addition, the results from a pharmacogenetic substudy of TRITON-TIMI 38 patients, as well as several early phase pharmacokinetic studies, showed that the active form of prasugrel does not appear to be affected by genetic variations in common cytochrome P450 (CYP) enzymes, including CYP2C19. Because both Effient and Plavix are “prodrugs”, they require CYP450 enzymes to convert them to their active drug form. Approximately 30% of Caucasians and 60% of Asians have reduced function in the CYP2C19 gene. Many drugs, including certain proton pump inhibitors such as omeprazole, also inhibit CYP2C19. As stated in the Plavix prescribing information, studies have shown that formation of clopidogrel’s active metabolite may be affected by patients with reduced CYP2C19 function or by drugs that inhibit CYP2C19, including certain proton pump inhibitors such as omeprazole.