Actos News

Challenges Ahead for Takeda Pharmaceuticals, Despite Judge's
Nullification of Jury Verdict
Thursday, May 2, 2013

A $6.5 jury award against Takeda Pharmaceuticals for failing to warn a California man and his physician of the risk of bladder cancer associated with Takeda’s diabetes drug Actos was overturned Friday by the presiding judge. But Takeda’s troubles may be just beginning.

The jury’s award was based upon two key findings. The first was that Takeda had failed to adequately warn plaintiff Jack Cooper’s doctor of the bladder cancer risk associated with Actos. The second was that Actos was the primary causative factor in Cooper’s cancer and hence, the failure to warn was a substantial factor in causing Mr. Cooper harm. The judge, however, nullified the jury’s verdict on the grounds that expert testimony had not reliably established that Mr. Cooper’s cancer was caused by Actos, and not other factors, such as his previous smoking history.

The judge did not question that Actos can cause bladder cancer. Rather he found that the opinion offered by a key plaintiff’s expert -  that Actos was the specific cause of Mr. Cooper’s cancer - was unreliable and did not meet standards for the admissibility of expert opinion set by a recent California Supreme Court Decision (Sargon v. USC, 57 Cal 4th 747 (2012). By ruling that the expert’s testimony was inadmissible, the judge effectively invalidated the jury’s finding that Actos caused Mr. Cooper’s bladder cancer, thereby nullifying the jury’s verdict.  However, the day after the judge issued his ruling based on Sargon’s having established a new California standard for excluding expert testimony, another Sargon opinion was issued by the court of appeals, Sargon Enterprises, Inc. v. University o/Southern California, (Sargon III) 2013 Cal. App. LEXIS 352 (Cal.App. 2d Dist. May 2,2013), which rejected the contention that a new standard had been established in Sargon I and reasserting that California’s prior expert gatekeeping standard remained in place.  This undermines the Cooper trial judge’s chief basis for striking the expert testimony. Also, once the jury issued its verdict, the standard the judge used for overturning the result changed to one more favorable to Mr. Cooper and the jury’s decision—under that standard, the judge would not be allowed to weigh any evidence, any evidence would have to viewed in a light most favorable to Mr. Cooper and any conflicts of evidence would be resolved consistent with the jury’s verdict as already evaluated and weighed by them.  Both of these issues are now the subject of post trial motions that will be heard on June 20 and may result in some changes to or reversal of the judge’s May 1 order.

Whatever the outcome of these new motions, the losing side is to appeal the judge’s ruling and it will be up to the appeals court to determine if the judge ruled properly. But regardless of the final outcome, there are several aspects of the case that are undoubtedly of considerable concern to Takeda going forward.

First is the inherently subjective nature of the judge’s ruling. Judges in subsequent cases may find the opinions of plaintiffs’ experts regarding specific causation to be perfectly admissible.

Secondly, the judge made no comment on the jurors’ finding that Takeda had failed to adequately warn Cooper’s doctor of the risk of bladder cancer associated with Actos. This also suggests that Takeda may have a difficult time prevailing in future trials where the link between Actos and the plaintiff’s bladder cancer is more evident, as in cases, for example, where the plaintiff has never smoked.

Equally problematic for Takeda is U.S. Supreme Court opinion on the responsibility of drug manufacturers to warn the public, which is unequivocal. In 2009, in Wyeth v. Levine, the court stated, “it has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market.”

But evidence offered at trial suggested that Takeda considered its primary responsibility to be the protection of its hugely profitable drug, which had $4.5 billion in sales in 2011. According to Dr. Howard Greenburg, a plaintiff’s expert on pharmacology and drug regulation and safety, Takeda had sparred with the U.S. Food and Drug Administration as far back as 1996, when rat studies indicated a link between Actos and bladder cancer. In a report prepared for the trial, Greenburg wrote, “The FDA reviewer noted that Takeda simply made conclusive statements that the connection between Actos and bladder cancer in rats was not relevant to humans.”

Nine years later Takeda’s pattern of denial had apparently not changed. At the time Takeda was faced with two studies, the PROactive study and a Northern California Kaiser Permanente study, that both offered evidence of a risk of bladder cancer linked to Actos. Several emails were exchanged among Takeda executives. On August 9, 2005, one executive wrote an email to Takeda’s President of Medical Research and Development, discussing the possible consequences of the new findings and presenting what he called a “worst case scenario”:

A more likely "worst case scenario" could be for the Agency to ask for an immediate label change incorporating bladder cancer findings, possibly some sort of a "Dear Healthcare Provider" letter to be sent, and posting of pioglitazone on the new "Drug Watch" portion of the FDA Web page.

Senior executive Kiyoshi Kitazawa wrote that “…we need to manage this issue very carefully and successfully not to cause any damage for this product globally.”

The emails illustrated what plaintiff’s lawyers argued was the predominant viewpoint at top levels of Takeda management: label changes, “Dear Healthcare Provider” letters, and anything else that might warn consumers of a link between their drug and bladder cancer were to be avoided.

These emails and other Takeda documents that illustrated the drug maker’s combative stance towards the Food and Drug Administration offered persuasive evidence that Takeda never intended to fulfill its legal obligation to warn physicians and consumers of the risk of bladder cancer associated with Actos. That pillar of the strict product liability and negligence claims – the failure to warn - remains in place and will loom large as Takeda begins defending itself against the thousands of Actos lawsuits that have been filed against the company.