Comments on: FDA Will Take A ‘Balanced’ View Of Enhance: Analyst

By: BWP MD

BWP MD — Wed, 09 Apr 2008 21:14:40 +0000

Paul,

Thanks for the perspective from MSP Marketing & Sales. As for Carotid IMT, you should look it up. This method has been used for two decades. There are innumerable studies correlating IMT thickness with CV risk, and big ones at that.

By: Paul

Paul — Mon, 07 Apr 2008 04:22:01 +0000

We all have to recognize:
- LDL is the current accepted surrogate marker because it has been demonstrated over and over — and regardless of method — to be a modifiable risk factor, i.e. the high higher the number, the higher the risk AND if you lower it, you lower the risk - with now “J curve”, meaning it has not been show how low is low

- Carotid IMT is an interesting marker of plaque formation BUT is not necessarily correlated to MI’s or mortality. It simply offers the best window into what may be going on in the artery wall. But there is a lot more to events, including inflammatory responses and other stuff.

- Vytorin claims that it lowers cholesterol. They don’t claim that it reduces hospitalization or mortality — even if it’s main component is the well-proven simvastatin.

All of this means that Temple is correct in his assertions. Nothing has changed.

If you need your LDL to come down a lot, then you can get high doses of Zocor, Lipitor or Crestor with risks of Rhabdomyalisis, or you can lower it with Vytorin. I’ll stay on Vytorin.

By: TALL16

TALL16 — Mon, 07 Apr 2008 01:32:23 +0000

After ENHANCE the FDA has to make a decision if they want lower LDL or not.

By: CVMD

CVMD — Sun, 06 Apr 2008 00:37:46 +0000

Temple needs to speak to the Metabolic/Endpcrine Division as they have been allowing companies to use Carotid Ultrasound IMT as one of their “gold standard” endpoints for years. All of the statin development programs have used this approach to try to obtain a “reduced progression of atherosclerosis” claim for their products. He should remember that ENHANCE was reviewed and negotiated with the FDA before it was ever started. he should also be reminded that MSP chose CUS IMT as their only study because they thought they could show a positive result in their stacked population. I’m sure they chose this route over Coronary IVUS, which would have been a much better choice. They made mistakes and that’s why they’re where they are. Particularly, since they apparently delayed the delivery of the negative results and profited by doing so.

By: Mike M

Mike M — Sun, 06 Apr 2008 00:03:31 +0000

Let’s all keep in mind that IMPROVE it will still fail to answer the real question, that is, does adding ezetimibe improve relevant outcomes when added to a statin alone, as Merck and Schering Plough are failing to include a cohort of patients who would receive 80 mg of simvastatin. By omitting the maximum dose of the statin, you are not truly assessing whether another agent needs to be added, you can still double the dose. When you see an inherent design flaw in a drug company study, it makes you wonder if it was placed there for a reason. Just throwing that out there.

By: Steven Walker

Steven Walker — Sat, 05 Apr 2008 11:43:37 +0000

I rarely agree with Bob Temple, but in this case, he is right. The word is still out on Vytorin, and he is doing what the FDA should do when individuals in medicine, and many in the press, over-react to a single clinical trial finding. Randomized trials are not nearly as definitive as the clinical trialing community (and sometimes the FDA)would like us to believe, nor did the Enhance trial ask or answer the question some seem to think was asked and answered. Everyone should take a deep breath on this one. The outocome of a trial designed to measure plaque buildup using an unvalidated measurement technique with accuracy and precision problems in heavily-treated patients with a genetic predisposition for high cholesterol and accelerated formation of plaque proves only that Vytorin is not in highlky obvious fashion the miracle drug its sponsor and many others hoped it would be. It is still a drug that has a dramatic effect on a valdiated endpoint, cholesterol lowering (and perhaps C-reactive protein), and there is no evidence anyone is being directly harmed by it. Our clunky, archaic staistical clinical trials system produces usable information at an agonizingly slow rate, so we will simply have to wait to find out how Vytorin will fit into the treatment scheme long term. Isn’t this really a reflection of just how insane the drug safety hysteria moevement has become when a drug that everyone agrees is safe and positively effects a well-validated endpoint for prevention and control of heart disease, becomes the center of a “scandal” for showing no discernible effect on something we are not even sure matters in a very difficult to treat population? Where is the scandal here? Why are people being told to stop taking this drug? We actually have no good reason to think that anyone should stop taking Vytorin. What I think we do know is that there are docs out there who know that creating and pumping up drug “scandals” boosts their careers, and media outlets who know that hyping them at the sound bite level sells their news product. Isn’t it time to get back to thinking about medicine and medical progress in a more rational and measured manner?

By: Justice in Michigan

Justice in Michigan — Sat, 05 Apr 2008 03:45:22 +0000

Bob Temple has a talent for talking in whatever direction appears convenient to him at the time.

If carotid plaque was not a particularly informative surrogate endpoint, why does anyone suppose MSP chose it?

And if Enhance had come out differently, does anyone think that MSP would also be in any way downplaying its significance?

I would suggest it would be all carotid, all the time.

And Temple would be saying …………. zilch.

By: Grieving

Grieving — Sat, 05 Apr 2008 00:11:32 +0000

Bob Temple? Is that the same Bob Temple that agreed with me at last June’s Medguide Hearing that Zyprexa (especially) but also the other atypical antipsychotics met all the criteria for having Medguides - another underutilized and overpoliticized drug safety tool - should have Medguides, as I testified?

And then, of course, did nothing……

By: G MD

G MD — Fri, 04 Apr 2008 20:32:05 +0000

Tim Anderson does not understand how the Part D providers work and set Tiers. He is a typical sell side analyst humping a theme. His personal agenda trumps the truth. Rah rah. Cheerlead that stock…..fool

By: Paul

Paul — Fri, 04 Apr 2008 18:10:15 +0000

Finally a sensible opinion.