Thursday, February 5, 2009

ENHANCE RICO Class Action Gathers Steam. . . .

Schering's lawyers (at Dechert LLP) had earlier filed motions to dismiss the portions of the Vytorin/Zetia Marketing, Sales Practices and Products Liability Litigation, formally captured under Polk v. Schering-Plough, et al. (Case No. 08-285), by suggesting that, among other matters, the FDA's jurisdiction forecloses RICO actions -- that only the FDA may bring such claims. Poppy-cock. So now, with much precedent in tow, the plaintiffs' lawyers have formally pled so. Let's read along, shall we?

. . . .[Schering-Plough's] argument about the FDA’s primacy in regulation of drug advertising (Br. at 23-26) rests entirely on their baseless assertion that the Complaint merely disguises violations of the Food Drug & Cosmetic Act of 1938, 52 Stat. 1040, 1042, 21 U.S.C. § 301 et seq. (“FDCA”), as civil RICO claims. Not only are Defendants wrong, but no court has ever invoked FDA “primacy” as a basis to dismiss a RICO claim based on predicate acts of mail and wire fraud involving suppression of material information and misrepresentations.

Here, the Complaint describes a scheme to suppress information, including the ENHANCE study results, bearing on the purported efficacy of Vytorin and Zetia. It does not allege FDCA violations as predicate acts or claims addressing the FDA’s regulation of prescription drugs. Rather, the RICO claim involves predicate acts of mail and wire fraud in furtherance of Defendants’ scheme to suppress material information. Defendants do not challenge the sufficiency of the pleading of those predicate acts. At this stage, those allegations must be accepted as true. . . .

Defendants ignore the numerous precedents upholding RICO claims alleging that pharmaceutical companies engaged in a pattern of racketeering activity involving fraudulent marketing of drugs through acts of mail and wire fraud. For example, in In re Synthroid Mktg. Litig., 188 F.R.D. 287, 289-90 (N.D. Ill. 1999), and 188 F.R.D. 295, 299-300 (N.D. Ill. 1999), the court certified a RICO class action where consumers alleged that they had paid increased prices for Synthroid because defendants, through predicate acts of mail and wire fraud, had suppressed a relevant medical study and falsely represented that other drugs were not Synthroid’s bioequivalent. Similarly, in In re Zyprexa Prods. Liab. Litig., 493 F. Supp. 2d 571, 574 (E.D.N.Y. 2007), the court upheld RICO claims alleging that defendants had misrepresented the safety and efficacy of the anti-psychotic drug Zyprexa via mail and wire fraud. And in In re Lupron Mktg. & Sales Practices Litig., 295 F. Supp. 2d 148, 167-68 & n.18 (D. Mass. 2003), the court held that the defendants’ fraudulent promotion of the cancer drug at issue was actionable under the mail and wire fraud statutes. . . .

The cases that Defendants cite (Br. at 24-25) do not suggest that Congress intended to preclude RICO claims alleging predicate acts of mail and wire fraud as a means to suppress information or convey false messages about prescription drugs. The alleged predicate acts in those cases were direct violations of the FDCA or other statutes vesting regulatory authority in a federal agency.

The Third Circuit has recognized that concealment of material facts by means of the mails or wires constitutes mail and wire fraud. United States v. Olatunji, 872 F.2d 1161, 1167 (3d Cir. 1989); accord United States v. Bryant, 556 F. Supp. 2d 378, 431 (D.N.J. 2008). That the FDCA creates no private right of action (Br. at 24) is irrelevant. Defendants cite no case in which similar allegations have been dismissed because of the FDCA. . . .

RICO, by its very design, reaches many of the same areas as do other statutes. Indeed, overlap is inherent in its scheme. See 18 U.S.C. § 1961; cf. Grove Fresh Distrib., Inc. v. Flavor Fresh Foods, Inc., 720 F. Supp. 714, 715-16 (N.D. Ill. 1989) (Lanham Act claim not an attempt to circumvent FDCA, where both FDCA and Lanham Act prohibited alleged misconduct).

Even assuming arguendo that there were an irreconcilable conflict between the FDCA and RICO, that would not suggest a repeal by implication because it is the more recent statute that normally controls. See Watt v. Alaska, 451 U.S. 259, 266 (1981). RICO was adopted more than thirty-two years after the FDCA. . . .

And so it would seem that the RICO counts in this putative class action complaint will move forward, inexorably toward a trial on the merits.

And that, coupled to the whiff of evidence that, while at the helm over at Pharmacia, about eight years ago, a prior Hassan- and Cox-led allegedly fraudulent truncated publication, and misleading partial disclosure of the Celebrex CLASS study results caused a securities fraud -- it will all begin to look very much like RICO repeated "pattern" activity -- trebling the potential damages, and very-likely ending two careers. We'll see.


Anonymous said...

We very well may have more instances.

Consider what recently occurred with Zyprexa. Now Lilly studied it in the elderly and it was included in the initial NDA however the indication was turned down due to Paul Lieber the Division Director of Neuropsych.

Now we all know Zyprexa is extremely cardiotoxic and kills the elderly who may be predisposed, and based on my analysis of the available public information I believe that it is extremely likely that this is due to a phen-fen like effect due to the 7-hydroxy metabolite and/or secondary metabolites of this. However the other drugs that are most similar to Zyprexa (olanzapine) are clozapine (Clozaril) and asenapine.

If scientists pre-phase III were really interested in this they would do a very good metabolism study to find out the metabolism and since 7-OH zyprexa is likely toxic to verify this for asenapine you would need to look for similar hydroxylated metabolites, i.e on ring on the opposite side of the molecule from the chloride for asenapine. In fact you wouldn't even need to wait for start human studies you could even do experiments to determine if human livers or enzymes produce these metabolits and you could check the effects in vitro. Toxicities in phase III human studies would only be icing on the cake. On the other hand if you suspected this and wanted to market something anyway you would do the exact opposite to hide any relevant data from the FDA.

Clozapine (Sandoz - now part of Novartis) turned out to be incredibly dangerous not only causing agranulocytosis but also causing lots of cardiac toxicity (e.g. heart attacks, etc.). Thus it is a drug of last resort if everything else fails and even then requires blood monitoring every few weeks to monitor agranulocytosis. Not to fear. Clozapine got on the market due to Fred's diligence.

Now Fred is championing asenapine. Now in October Condor posted my comment about Pfizer walking away. Yet Fred stated 7 months earlier that he knew Pfizer walked away from it. Although he indicated it was because Pfizer already had an antipsychotic Geodon (which everyone knows is a dog). Even Reuters headline indicated Hassan's support for asenapine was tepid.

So adding a more efficacious drug with a psych sales force already in place wouldn't be a problems especially after spending
a 1/4 billion or up on asenapine wouldn't have been a problem for Pfizer.

Now look at Freds' History.

Clozapine - Sandoz - 1989 agran and cardiotoxic sold. 1996 merger to become Novartis

Phen-Fen - Wyeth 1997

Celecoxib (Celebrex) - Searle Subsidary of Pharmacia 1999 - Merged with Pfizer

So we have Fred with a history of championing very cardiotoxic drugs at a variety of companies. and then jumping ship usually with the company being merged into another. Now if you were going to intentionally do this wouldn't you want the same people helping you who you can trust.

Now this time we have NIMH pushing antipsychotics in children. Plus ~1 week after the filing of asenapine is announced you have FDA announcing the off-label promotion guidance. Then 2 days before the asenapine approvable letter is announced you have the off-label promotion guidance officially implemented.

Now why would anyone hire a pricey specialty sales force for asenapine alone when you could outsource it much cheaper. Unless of course you thought that the extra expense was going to pay for itself via increased sales. Now how could that happen? Well a psych sales force might also go to child psychiatrists and push off label based on an NIMH positions that kids with ADHD who continue to show irritability (100% of kids with ADHD) need to be on antipsychotics to prevent the development of bipolar disorder (a hypothesis). Now if you paid an outside sales force there might be too much documentation that this was occurring, however an inside sales force would be much easier to hide inappropriate marketing.


Anonymous said...

It's an interesting concept that FDA jurisdiction preempts RICO.

But who's watching the watchers?

If SP is involved in racketeering who's to say that the same isn't occurring inside of FDA. Just look at what occurred recently with the 9 CDRH (device) reviewers.

As for suppression of material facts by wire. Well I have some questions for FDA.

What about Tom Laughren's statement in the press last Sept 2nd that there's NO hypothesis for why Chantix causes suicide. There's a big difference between NO HYPOTHESIS, and I don't agree with the hypothesis that is being presented, or even I don't even want to look into it when someone claims they do have a hypothesis.

What about the approvable letter for asenapine for schizophrenia. Even SP acknowledged that in 2 of the 4 efficacy studies asenapine didn't work, and a 3rd was a failed study. So Dr. Laughren (division director of psychopharmacologic drug products) how can you have 2 adequate and well controlled studies when the sponser indicates in their own press releases that they only had one?

Now these are only 2 examples but if there are 2 who knows, perhaps there's more.

Anonymous said...

As we know asenapine is very similar structurally and pharmacologically to another one of Fred's drugs clozapine.

So if you want to get an idea of cardiac toxicities with asenapine before even starting studies you need to look at what clozapine does.

The easiest way to do this is to look at FDA documents (although in general FDA always downplays safety issues).

Well clozapine has 5 different black box warnings.




3. FATAL MYOCARDITIS esp. in first month



(comment: other psychotropic drugs like an SSRI perhaps)


(inflammation of the heart which could be a term that could be used to describe the inflammation that occurs with phen-fen prior to scarring fibrosis)

In addition, FDA has a guidance on conducting bioequivalence studies with clozapine. In fact it's the only drug with such a guidance. Now why should that be? Well just look at following from the introduction to that guidance.

"Because a high number of healthy subjects experienced serious adverse effects such as hypotension, bradycardia, syncope, and asystole during clozapine bioequivalence studies, FDA is recommending that studies not be conducted using healthy subjects."

"In addition, a single-dose study using a 12.5 mg dose is no longer recommended. Instead, this guidance recommends a multiple-dose bioequivalence study conducted in patients using the highest dosage strengths (e.g., 100 mg tablets)."

In other words the cardiac toxicities are so serious (i.e. your heart may simply stop) that FDA is scared sh--less that even a slight increase in bioavailability within the upper limit of 125% (for an average) might result in death. Consequently, let's do a multiple dose study to maximize the chance of finding the generic company whose drug has problems.

Now it's obvious from clozapine's black box warnings and that fainting (syncope) might be a symptom of this. Now Zyprexa long acting was turned down because of excessive fainting and somnolence, and just this week Riperdal Consta was also made approvable due to fainting with the injection.

Hmmm. All this points to a similar mechanism with differences in pharmacology due to differences in possibly a toxic contaminant in the liquid formulations and/or a difference in metabolite and/or parent drug exposures on using a parentaral route where oral administration might otherwise protect you.

Also look at the recent approval of Effexor's (venlafaxine's) active metabolite Pristiq (desvenlafaxine or N-desmethyl - Just like Pfizer warns us about). It was held up as approvable forever. Then when it was approved the labeling has over a 5% incidence of cardiac side effects in short term studies. (Remember labeling FDA guidances last year changed reporting of side effects to only those 5% and double placebo).

So do we have a class effect? If so, how dangerous is asenapine compared to others?

Now asenapine is SL and isn't swallowed either (except in kids and those who cheek the med). So do we have a higher risk with SL asenapine? If this risk is dose related is it higher in little kids who will swallow proportionately more from a sublingual tablet. And what happens when kids are already overdosed when administered adult strengths off-label?


Anonymous said...

You know what's really disgusting. FDA even had an advisory committee on the syncope issue with Zyprexa in Feb 2002 and attributed it to Neurally Mediated Reflex Bradycardia. What a convenient explanation. This way you can explain away any cardiac toxicities like asystole you see in phase I healthy volunteer studies where you have cardiac telemetry.

But if you see syncope or worse asystole why wouldn't you have the cardiologist do a complete workup for NMRB.

Because if they did and it clearly wasn't due to NMRB then you wouldn't have an excuse to use to explain away a major lethality issue.

Anonymous said...

Lilly even has a name for the side effects that occur with Zyprexa long acting injection:

Post-Injection Delirium/Sedation Syndrome (PDSS)

This is how Lilly describes it: patients experienced and recovered fully from which describes a range of signs and symptoms such as sedation, delirium, dizziness, confusion, disorientation, slurred speech and altered gait.

Now the following from the labeling of pergolide which was removed from the market for causing a phen-fen like cardiac valvulopathy

"patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with Pergolide mesylate such as concomitant sedating medications of the presence of sleep disorders. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require participation (e.g., conversations, eating, etc.), Pergolide mesylate should ordinarily be discontinued."

Now is this just non-specific sedation or is it due to an effect on specific CNS serotonin receptors and if so are they related to effects at any other serotonin receptors?