Billion-dollar settlement of Paxil birth-defect lawsuits

Only a week after Glaxo SmithKline (GSK) agreed to pay $460 million to settle over 10,000 personal injury lawsuits related to Avandia,  it was reported that GSK has agreed to pay $1 billion dollars to settle  800 cases related to birth defects caused by  the GSK anti-depressant Paxil, taken by pregnant women. Both of these settlements are part of the $2.4 billion GSK has set aside to resolve pending litigation, according to corporate filings last week.

This $1 billion Paxil settlement will provide an average payout of more than $1.2 million to each family of an affected child, many of whom are left with heart defects as a result of their mother taking the drug. However, this settlement leaves more than 100 related cases still pending.

This settlement also follows a recent trial in Philadelphia, where a jury awarded a family $2.5 million for their child’s heart birth defect caused by Paxil. That lawsuit revealed internal “Glaxo documents showing executives talked about burying negative studies about Paxil’s links to birth defects and that its own scientists were alarmed by the rising number of children who had been affected by the drug in the womb.”

These recent settlements, combined with  earlier ones related to allegations that Paxil caused suicide, attempted suicide, and addiction, brings GSK’s total settlements on Paxil to over $2 billion so far.

Yet GSK sales of Paxil, one of the true blockbuster drugs in the last 15 years, generated $11.7 billion in US sales between 1997 and 2006. So GSK has profited dramatically from this drug, while leaving a wide trail of shattered lives and grieving families.

Despite these settlements and the 2005 black-box warning the FDA added to the drug’s label on increased risks of suicidal thoughts among adolescents, Paxil still earned $793 in sales in 2009.  It continues to be one of the more profitable drugs on the market.

Avandia study suspended, conflicts revealed

In a statement released yesterday, the FDA placed the TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation) study comparing Avandia with its rival Actos on a “partial clinical hold.” This means that no new subjects can be enrolled, but that existing subjects can continue to participate.

This decision by the FDA is not all that surprising since, even though the FDA’s Advisory Panel voted 19-11 last week to recommend that the study continue, there was at least one member of the panel who questioned whether it was ethical to continue this study in light of the known serious cardiac risks.

Though the FDA had previously stated that they issued no conflict of interest waivers for the advisory panel hearing last week, two conflicts have since come to light. David Capuzzi, an endocrinologist on the panel, earned $3,750 last year (and $14,750 in total) as a speaker for another GSK drug, Lovaza. Though Dr. Cappuzzi denies he ever spoke about Avandia, a GSK spokesman reported that at least one of Capuzzi’s talks prior to 2008 was on Avandia. It is noteworthy that Dr. Capuzzi defended Avandia during the advisory panel hearing and voted to keep it on the market despite the fact that he claimed he rarely prescribes Avandia as he does not “like the whole class of drugs” and prefers to prescribe metformin.

Dr. Capuzzi explained his failure to disclose by saying that “the FDA doesn’t consider a different product for the same company to be a conflict of interest.” He furthermore said that he did not disclose this information to the FDA because he was never asked about it.

…. Really?

Pharmalot (hat-tip) reports that the FDA policy requires that panel members “report all current financial interests and those held within the previous 12 months that could be affected by the discussion and outcomes of the meeting, or that would present appearance issues.”

The FDA went on to say that they “take these allegations [against Cappuzzi] very seriously and [are] investigating the matter.” Additionally, Pharmalot reported that an FDA spokeswoman stated that “a decision [on their investigation] is expected by the end of the week and, if the agency determines there was misconduct, the matter could be referred to the HHS Office of Inspector General.”

On the flip side, the Wall Street Journal reported yesterday that Abraham Thomas, a doctor who voted to take Avandia off the market, was a paid spokesman for Takeda, who produces Avandia’s rival drug, Actos. Dr. Thomas was a member of the Takeda Diabetes Speakers Bureau from September 2007 to September 2008 and received $5,000 for giving two presentations. It is currently unclear if Dr. Thomas will be investigated by the FDA as well, since his relationship with Takeda took place over a year ago.

Ultimately, other panel members that have been interviewed do not feel that these conflicts of interests affected their decisions. One stated, “the panelists came prepared and had very strong opinions [that] won’t be easily swayed by other people’s opinions unless they’re very compelling,” but one panelist did say that the FDA “encourage[d] us to err on overdisclosing  [and]  to disclose anything in [our] past that may have relevance.” You would think that a paid relationship with the pharmaceutical company in question, or one with the drug’s  major rival in its class would be relevant enough a potential conflict for someone to disclose.

Panel decision-making warrant scrutiny 

 Finally,  in even more news to cause the public to question the reasoning methods used by the Avandia advisory panel, it was recently reported by the USA Today that at least one of the 10 advisory panel members who voted to keep Avandia on the market with tight restrictions says he’d actually prefer that the FDA withdraw it. This panelist, Clifford Rosen, has publicly stated that the only reason he didn’t vote to withdraw Avandia from the market is because he was “very anxious” he’d be the only one to vote that way. Dr. Rosen, who chaired the 2007 advisory committee meeting where panelists voted 22-1 to keep Avandia on the market despite the cardiovascular risks associated with the drug, says that he and the 21 other panelists who voted to keep the drug on the market  did so because they did not know whether Actos may be even riskier. Despite his previous vote, Rosen has stated that he has not prescribed Avandia since this 2007 meeting.

 After all this, we clearly haven’t heard the last on Avandia ….