Whistleblower Suit Claims Pioglitazone Cover-up

Suit Implicates Dr Steven Nissen, Cleveland Clinic

Shelley Wood

May 10, 2012

May 10, 2012 (Boston, Massachusetts) — Lawyers representing Takeda Pharmaceuticals have one more day to either file an answer to or challenge the validity of a whistleblower suit centered, in part, on the underreporting of congestive heart failure (CHF) events with the company's diabetes drug, pioglitazone (Actos).

Dr Helen Ge, a former employee at Takeda, alleges that false claims for payment were made to Medicare and other federally funded healthcare programs on the grounds that the company "was able to capture a majority of the diabetes drug market by falsely portraying Actos as safer than it actually was."

"But for Takeda's fraud, government healthcare programs would have paid for substantially fewer Actos claims" and physicians would have prescribed it less, the whistleblower suit alleges.

Suit goes it alone

Ge's qui tam suit, launched in June 2010, is seeking damages and civil penalties from Takeda on behalf of the US government; her attorneys are proceeding with the litigation, despite a decision by the feds and the 25 states with similar false claims act legislation to decline to intervene in the case.

One of Ge's lawyers insisted to heartwire that it is "not unusual" for government to decline to intervene; in this case, the Justice Department spent a year and a half reviewing the case before opting out, attorney Michael Baum explained.

The feds will continue to monitor the case, and if litigation is successful or if discovery turns up information that changes their minds, "they might intervene earlier," Baum said. "Our view, having worked on a lot of pharmaceutical cases and having a pretty good idea from our whistleblower what things we will find in discovery, we feel that the case should proceed and we should conduct discovery, and discovery will bear out Dr Ge's allegations."

Ge's lawyers hope to "obtain internal emails and publication plans and marketing plans that will provide further support to our contentions in the complaint," Baum said.

Underreporting of known, serious side effects

Ge's suit alleges that Takeda failed to properly report CHF cases to the FDA and instructed medical reviewers, Ge included, to not report hundreds of nonhospitalized or nonfatal CHF cases as "serious" after the boxed warning was added to thiazolidinedione (TZD) drugs in 2007.

Only "serious" adverse events for older drugs end up in the FDA's Adverse-Event Reporting System, the suit alleges, thus boosting the company's alleged aim of positioning its drug as safer than rosiglitazone.

Ge says her contract with Takeda was terminated after she complained to three superiors about the downgrading of CHF events. Her suit also states that the number of CHF reports dropped dramatically in 2010, after she was fired from the company, despite rising sales of the drug.

Ge's suit also details alleged cover-up of reports of other adverse events, including cancers, suicidal ideation, renal failure, and cardiomyopathy, among others.

Financial conflicts alleged with Nissen, Cleveland Clinic

Ge's suit names only the pharmaceutical company as defendant but does allege that financial connections between the Cleveland Clinic's Dr Steven Nissen "should be considered when analyzing Actos's risks compared with Avandia's."

Nissen, with Kathy Wolski, famously published the rosiglitazone meta-analysis that set off the TZD firestorm, showing a 43% increase in MI with pioglitazone's chief competitor. Ge's suit cites the Nissen paper as a key factor in Takeda's efforts to position pioglitazone as a safer alternative to rosiglitazone. Nissen, the suit notes, was principal investigator for the phase 3 PERISCOPE trial, which used intravascular ultrasound (IVUS) to screen patients for trial eligibility, then repeat IVUS imaging for trial participants. Ge's suit estimates that "payment Nissen received from Takeda through Cleveland Clinic Foundation was estimated to be $8 million to $10 million" for PERISCOPE and that IVUS procedures likely brought in over $13 million in revenue for the Cleveland Clinic.

Pharmalot, which reported Ge's original suit in early March, quotes Nissen as pointing out that Ge's calculations were off base, since reimbursement would have been divided among all of the enrolling centers, of which there were more than 100 globally.

Contacted by heartwire yesterday, Nissen characterized the lawsuit as old news and called the claims "total nonsense," stressing that he "got not one dime."

Asked about the millions allegedly made by his institution, Nissen said that the Cleveland Clinic, as well as the Duke Clinical Research Institute and other academic research centers, "do clinical trials and the institutions get revenue, but that is completely irrelevant to this lawsuit."

He notes that Takeda funding for PERISCOPE was disclosed in the JAMA article and "there is nothing there that has not already been in the public domain for years."

Nissen also points to the fact that the Justice Department and 25 states had declined to intervene. "They did not find any merit in this, and they refused to try the suit. So the thing, as far as I can tell, is completely dead."

Hundreds of millions?

Baum, however, points out that the government opts not to intervene "in most cases and has stated that that does not mean the case has no merit. . . . They are relying more and more on the private sector to litigate the case to begin with and wait and see what discovery turns up."

Baum also stressed that Nissen "is not a party; he is identified because he was working on the PERISCOPE trial [with Actos] on behalf of Takeda at the same time he was conveying this information regarding Avandia. And we want to see what communications occurred between Dr Nissen and Takeda and see what information Takeda was funneling to him."

If successful, Ge's suit could see her stand to win 15% to 30% of the civil settlement in the case. Her lawyers would not put a number on this, but the suit itself estimates that the government has "suffered hundreds of millions of dollars of damages."

Takeda has not responded to heartwire 's request for comment; the company will need to file its response to Ge's claim tomorrow. The company had previously asked for--and was granted--an extension to an earlier response date last month.