Takeda Allegedly Hid Adverse Events, Whistleblower Says

Takeda Allegedly Hid Adverse Events, Whistleblower Says

March 12th, 2012 // 1:05 pm @

Source: Pharmalot

Takeda Pharmaceuticals may wish that Helen Ge was never hired as a consultant. She has now filed two whistleblower lawsuits alleging the drugmaker knowingly hid adverse events about various drugs. One lawsuit involved the Uloric gout treatment, which we recently reported (read here). Yet another concerns the Actos diabetes drug and a failure to report instances of bladder cancer and congestive heart failure.

Ge, for those who may not recall, was hired as a medical reviewer in the pharmacovigilance division. And by her account, she was quite vigilant, but her colleagues were not. And so, when she repeatedly raised a fuss about alleged discrepancies and shortcomings in reporting assorted and sordid adverse events, she was shown the door. The whisteblower lawsuits followed.

The lawsuit concerning Actos was unsealed last week after the feds declined to intervene, or join, the proceedings. As with the episode concerning Uloric, she alleges a similar pattern. Ge was reviewing adverse events for Actos and noticed that an internal database recorded 100 cases of bladder cancer, but the number reported to the FDA was 72, which she termed a “serious discrepancy.”

So what happened when she informed her supervisors? She alleges that they directed her to change her assessment from ‘related’ to Actos to unrelated. Meanwhile, she also charges that carcinogenesis resulting from the diabetes med was discovered during initial animal studies and later confirmed during Phase III testing. Ge, in fact, charges Takeda amended patient enrollment criteria to yield favorable results (see page 34 of the lawsuit).

This is, of course, potentially damaging to Takeda. The drugmaker already faces hundreds of lawsuits over concerns that taking its pill for more than a year raises the risk of bladder cancer. Last June, Takeda halted sales in Germany and France after pressure from regulators. Since then, the FDA and the European Medicines Agency have issued warnings, although the drug remains available (see here, here and here).

We asked Takeda for a response and will update you accordingly.

Separately, Ge also alleges that Takeda failed to properly report all congestive heart failure adverse events related to Actos to the FDA between 2007 and 2010. Her lawsuit claims the drugmaker “instructed its medical reviewers not to report hundreds of non-hospitalized or non-fatal congestive heart failure cases as ’serious’ adverse events and thus avoided its responsibility of accurately analyzing and reporting these hundreds of serious adverse events to the FDA.”

On a related note, Ge goes on to maintain that Takeda “orchestrated” the Avandia downfall. Avandia, of course, is the rival GlaxoSmithKline pill that is in the same class of diabetes drugs, but was linked to serious cardiovascular risks and its usage was significantly restricted by the FDA (look here). In her lawsuit, she attributes some of these developments to Cleveland Clinic cardiologist Steve Nissen.

Nissen, you may recall, authored a 2007 meta-analysis that raised cardiovascular concerns about Avandia. Ge reiterates previous reports that Nissen was also a principal investigator for a Phase III Actos trial and an imaging procedure he invented and was used in the trial may have generated about $13 million in revenue for his institution, according to her calculations. In her view, though, Actos was an equally troubled drug and to allow Avandia to be singled out as the “bad” drug is “unconscionable,” according to the lawsuit. We asked Nissen for a response as well and will update you.

[UPDATE: We heard back from Nissen and he wrote us this: “I don’t accept any honoraria or other reimbursement from pharma or device companies with no exceptions. That policy was applied to Takeda. Of course, we do perform many clinical trials (including Periscope), but there is no personal income associated with such research studies. The funding of Cleveland Clinic to conduct Periscope was disclosed in the original NEJM Avandia manuscript and all other communications. As you know, our analysis of Avandia ultimately proved correct and the drug is now virtually gone worldwide. It’s hard to argue bias when there is no income involved and the analysis was ultimately proven to be correct.”

He adds that Ge calculated the reimbursement for the trial incorrectly. Reimbursement for the imaging procedure went to the enrolling center, and there were more 100 centers in a global trial, although the Cleveland Clinic was not an enrolling center. Ultimately, reimbursement was distributed to the centers based on enrollment. “We were just the academic and scientific lead,” wrote.]

In any event, as a result of downplaying and hiding adverse events, Ge claims countless prescriptions for the Takeda drugs were written unnecessarily, causing Medicare and Medicaid to overpay for the medications. “Takeda’s fraud has caused tens of thousands of false claims to be made on federal and state health care programs,” causing “hundreds of millions of dollars” in damages, the lawsuit states.

[UPDATE: A Takeda spokeswoman sent us this: “Takeda is aware of Dr. Ge’s lawsuits. Given that these lawsuits are pending, we cannot comment on plaintiff’s specific allegations. However, Takeda complies with all laws and regulations regarding the reporting of adverse events.]

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