In a letter-brief filed with the court just yesterday, Ezra D. Rosenberg, of Dechert LLP (Schering's law-firm in Polk, one of the most-important ENHANCE-related putative class actions -- the sales practices and marketing action, Case No. 08-cv-285) urges Judge Cavanaugh to mis-read the FDA's updated safety announcement on Vytorin/Zetia -- as an efficiacy announcement.
Dechert suggests, entirely-erroneously, in its brief before Judge Cavanaugh, that the FDA SAFETY Announcement affirms Vyorin's efficacy. It does no such thing, and I strongly suspect Judge Cavanaugh will sniff this out, immediately. Take a look at the title of the FDA document at issue: "FDA Issues Update to Safety Review on Cholesterol-Lowering Drugs". Safety -- safety -- safety, not efficacy. Sheesh; really.
Dechert goes on to quote this portion of the FDA Announcement (but simply omit the title of the document):
. . . .Preliminary results from ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) had indicated there was no significant difference between Vytorin and Zocor-treated patients in the thickness of the walls of the blood vessels of the neck (the carotid arteries) although there was greater lowering of the amount of LDL cholesterol in patients with Vytorin compared to Zocor.
Measuring the thickness of the carotid arteries via ultrasound imaging is considered a biomarker of risk for cardiovascular disease.
FDA has now completed its review of the final clinical trial report of ENHANCE. After two years of treatment, there was no significant difference in carotid artery thickness between Vytorin patients and Zocor patients. However, the levels of LDL cholesterol, decreased by 56% in the Vytorin group and decreased by 39% in the Zocor group. . . .
That is precisely the opposite of an efficacy finding. All FDA said was that Vytorin was not definitively unsafe. [Full Dechert letter-brief-filing here, as a PDF file.]Mechanism of action will prove to be everything, here.
I guess Dechert only listened to the less-well-informed members of the fourth-estate (and the spin-meisters in Kenilworth).
Dechert goes on to make thinly-veiled preemption noises, using the FDA Announcement as fodder, but those seem unavailing, given the firm's misreading of the actual purpose of the FDA's statement last week.
This is, honestly, sort of surprising. Are there no ex-scientists among the lawyers at Dechert? Wild.
6 comments:
Condor, your logic is a bit flawed. Re-read the FDA statement. It urges patients to NOT STOP taking Vytorin without talking to thier doctor. The FDA isn't in the buisness of encouraging drug use just because the drug is safe. So what? If drug must be safe AND have reasonable evidence of efficacy. The fact that the FDA does not want to people to discontinue use is an implicit affirmation of its efficacy. (or at least an implicit affirmation of the biomarker being utilized for efficacy - cholesterol levels)
Here's the FDA statement: "Based on currently available data, patients should not stop taking Vytorin or other cholesterol-lowering drugs and should talk to their doctor or other health care professional if they have any questions about Vytorin, Zetia or the ENHANCE trial."
The "efficacy" on which Vytorin is approved and reccommended is cholesterol reduction. In that sense, the "efficacy" of Vytorin was actually reaffirmed by the ENHANCE trial. The FDA has no reason to doubt the efficacy of Vytorin. What they *DO* have reason to doubt is whether or not cholesterol reduction (by itself) is really a valid "efficacy" that we should be aiming for. Thier safety statement re-affirms that (for now) the FDA believes that cholesterol reduction is benificial even without proof of "clinical benifit". (ie reduction of heart attacks, mortality, etc)
Nathan -- Welocme back!
I do think your observations are generally valid -- but in the context of presenting what will amount to evidence in federal court, it is my opinion that it was unwise for Dechert to cast an FDA SAFETY update as an endorsement of the drug's EFFICACY.
FDA plainly did NOT say that the mechanism of action -- the gut mechanism employed by Zetia/Vytorin -- improves CV risk outcomes.
But that is what the Schering ads CLAIMED, up until January of 2008. And that is one of the central claims of the Polk suit. The Ad was deceptive -- and Schering knew it.
I think this overly-aggressive style of legal grandstanding will not serve the Schering shareholders well, in the longer run.
The judge will see through it -- it seems a rather ham-handed, cheesey tactic.
Perhaps "Okay", on the very margin, for ad copy (pre-January 2008) -- not at all PROBATIVE, as a legal defense, in a court of law -- in January 2009.
Namaste
Oh, but the FDA statement IS all about the efficacy. I saw precious little regarding actual safety.
The FDA says lowering LDL corresponds to lowering the relative risk of cardiovascular events. What did Vytorin (Zocor and Zetia in one pill) do in the ENHANCE study? Lower LDL 56% when Zocor alone lowered LDL only 39%. I believe this would amply satisfy that hankering for efficacy, or effectiveness, yes?
The (end)point of this study was not to count MIs, CVAs, CABGs, or corpses. It was about changes in plaques and lipid parameters in patients who had an LDL (not Total Cholesterol but LDL) above 300mg/dL.
When it comes to plaque in these patients, neither treatment seemed to work so well. But for lowering LDL, the numbers suggest that two drugs are better than one.
So, the FDA says lower cholesterol is better but they have yet to determine if how that mission is accomplished really matters. I guess we will see if they take a stand on that issue when they finish sifting through the epidemiological data from the SEAS trial.
Again, Nathan (I presume) --
This is now about what will be evidence in a federal court.
The latest FDA Announcement was, by its terms, about declaring Zetia/Vytorin "not unsafe".
Dechert's touting it as evidence of efficacy, in a court of law, has "opened the door" -- to allow the plaintiffs to counter that notion -- and prominently highlight the FDA's earlier formal letter characterizing Schering's Vytorin ads as "misleading" and "deceptive" -- given the ENHANCE results.
One of the central claims of the Polk putative class action suit alleges the ads were false, and thus "deceptive".
It seems that the FDA agrees.
Net result? Not good for Schering -- in a court of law.
Namaste
As Bob Temple said ENHANCE is not an event trial come back later. CIMT means nothing from efficacy, yes LDL prevents CV events but ENHANCE is meaningless.
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