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Friday, July 31, 2009

The Effient Launch: Cracking the Door to Primary-Care Marketing

So will personalized medicine be the death of primary care? Maybe not. Maybe just the opposite.

In this edition of the IN VIVO Blog Podcast, Mike McCaughan, our editor-in-chief, gives a decidedly positive (albeit counterintuitive) spin to what some of us in the editorial group thought was a pretty obviously bad piece of news: Effient’s black-boxed approval last July 10.

Yes, Effient (prasugrel) had beaten the competitor, Sanofi/Bristol-Myers’ Plavix, in Lilly’s head-to-head pivotal trial (fewer heart attacks and strokes for Effient’s users, though more bleeding) but still, we wondered, would Lilly – which depends on Effient to get it past the Zyprexa cliff – be able to build much competitive momentum against Plavix while dragging along its black-box warning about bleeding? And even if it manages to gain that momentum, won’t it be stopped dead in its commercial tracks when Plavix goes generic in 2011?

Mike’s notion: that the black-box warning and mandated two-year REMS requirement create the basis for primary-care marketing success – thanks to pharmacogenetics. Not because the data suggests the right population to get Effient – but because it argues that a third of the population getting Plavix get no benefit from it (an argument the FDA evidently agreed with because it added it to Plavix’s label). Lilly reps thus get an FDA-mandated foot-in-the-door to talk to docs about Effient’s risks (and Plavix’s deficiencies)…and, within two years, face a generic with no marketing effort behind it that they will argue doesn’t work in a third of a very high-risk population.

So click below to hear Mike’s full explanation (or you can access the podcast via iTunes).








Image from Flickr user twenty questions and used under a Creative Commons license.

5 comments:

Anonymous said...

These guys obviously haven't read the actual study bringing Effient to market. The lead investigator of the study wrote a letter to the FDA telling them that the study was not set up correctly and that it shouldn't be approved based on the study results. The dosing and administration was not equivalent for Plavix and Effient and when the results of the OASIS trial come about (600mg loading dose of Plavix vs 300mg that was used in the Effient trial) the results won't hold any water what so ever.

JONATHAN said...

In response to Anonymous,

You obviously haven't read PRINCIPLE-TIMI 44 where investigators compared a 600mg loading dose of Plavix to a 60mg loading dose of Effient. The results showed greater levels of platelet inhibition in the Effient group. TIMI 44 also studied a 150mg maintenance dose of Plavix vs. a 10mg maintenance dose of Effient. Yes, my friend, Effient was still more efficacious in the maintenance phase too. Hope you're still able to hold your water. Good luck.

smileyface said...

Well Jonathan, PRINCIPLE-TIMI 44 was a pharmacokinetic study which has very little bearing on clinical results. May I point out to you that another very important clinical trial CHAMPION was stopped prematurely in May 2009because another very potent ADP inhibitor-Cangrelor(which produced even more rapid and greater platelet inhibition than prasugrel) demonstrated no benefit when compared to clopidogrel 600 mg.in PCI patients. Check this out on Cardiobrief using the Search icon. Moreover, how come you forgot to mention about the serious bleeding problems that prompted the FDA to mandate a BLACK BOX warning? And what about the REMS that the FDA has mandated for 2 years. Did you actually read the TRITON editorial?-- 'For every CV death prevented, there was one additional FATAL bleed'.This leaves cardiologists with a terrific choice, right?.

Anonymous said...

Yes, smileyface, TIMI-44 was powered to show superior inhibition of platelet aggregation alone. This is because the TIMI-38 hypothesis was proven that greater inhibition of ADP-IPA by means of the tested regimen of clopidogrel is more effective at preventing ischemic events than is the inhibition conferred by a standard regimen of clopidogrel. So TIMI-44 needed only to prove that Effient would continue to show greater levels of inhibition when compared to higher doses of clopidogrel.

The bottom line is that for every 1000 patients treated with Effient as compared with clopidogrel at the doses studied, 23 MI's were prevented, with an excess of six non-CABG-related TIMI major hemorrhages. So the question becomes, would bleed rates go up when using a 600mg loading dose of clopidogrel and a 175mg maintenance dose? I think so.

As for the black box and REMS, I wasn't avoiding it. It just wasn’t' a part of the discussion. We were talking about loading and maintenance doses. But since you brought it up, the concern with TIMI Major Bleeds are legitimate, but it can be minimized by following the guidelines set forth in the Effient Prescribers Information (PI). That, after all, is why there is a black box! Follow it and you will know where to use Effient and where to use clopidogrel. Keep that smile up!

Anonymous said...

The Oasis 7 study is bogus. The study showed no difference in the dosing regimens in regards to the primary endpoint. They then took the pts. who went on to PCI and showed that efficacy was better, with a higher rate of bleeding. Plus, the curves start to diverge at day 7, and its only a 30 day study. Effient is a great drug for diabetics and STEMI (greater efficacy and no addt. risk of bleeding). If you look at the actual belleding data, both drugs had higher rates of bleeding for all comers. When the >75 and <60 kg were exluded, the rates for both cohorts were cut in half. Bottome line..great product if uses in the right pt.