More Damning Evidence Against GSK and FDA on Rosiglitazone

From Heartwire

Sue Hughes

July 13, 2010 (Washington DC) — Further evidence has come to light suggesting that GlaxoSmithKline knew about an increased cardiac risk with the diabetes drug rosiglitazone (Avandia) as early as 2001 but withheld the data and that certain officials at the FDA conspired with the company to minimize the impact of later safety results. The news comes on the same day that the FDA advisory panel starts its two-day hearing on the cardiovascular safety of the drug.

The findings are from a deposition from a former manager in the FDA's drug-safety unit to lawyers suing GlaxoSmithKline and from several emails to and from company employees discussing the negative results and the need to keep them quiet. These have surfaced as part of the inquiry by Sens Charles Grassley (R-IA), and Max Baucus (D-MT) into Avandia [1].

Dr Rosemary Johann-Liang, the former FDA drug safety manager, left the FDA in 2007 following her recommendation that GlaxoSmithKline add more information about health risks to Avandia's label, a Bloomberg report notes [2].
It adds that the FDA waited 17 months after Johann-Liang's recommendation before implementing a safety warning and excluded her from safety review meetings.
In her deposition, Johann-Liang stated that FDA officials provided the company with details of internal agency discussions about strengthening the warnings.

An email obtained by the New York Times implicates Dr John Jenkins, director of the FDA's office of new drugs, in the matter [3].
The email from a company official states: "It is clear the office of new drugs is trying to find minimal language that will satisfy the office of drug safety." Johann-Liang is reported to have testified that the leaks "should not have happened" and violated FDA policy.

Other emails document internal conversations at GlaxoSmithKline about concealing cardiac results with rosiglitazone.
In one 2001 communication, Dr Martin I Freed, a GlaxoSmithKline executive, answering a question about possible publication of the data, wrote: "Not a chance. These put Avandia in quite a negative light. . . . It is a difficult story to tell and we would hope that these do not see the light of day."
Another email from Freed, talking about concealing the data, says: "This was done for the US business, way under the radar," adding: "Per sr mgmt request, these data should not see the light of day to anyone outside of GlaxoSmithKline."
Another document was reported to estimate lost sales if Avandia's cardiovascular safety risk "intensifies" at "$600 million from 2002 to 2004 alone."

GlaxoSmithKline denies concealing data. A company spokesperson said the comments quoted had been "intentionally taken out of context" and that the company has been entirely forthcoming with the FDA and the Senate committee. "Cherry-picking a handful of documents from more than 14 million pages of documents distorts the record and is misleading," she added.

Glaxosmithkline Says Reports Are "Cherry Picking"

GlaxoSmithKline said the documents released by the Senate Finance Committee have been taken out of context and are therefore incomplete and misleading [4].
It says one of the studies discussed was looking at the effect of pioglitazone (Actos, Takeda Pharmaceuticals) on LDL and triglycerides; it was not a study on rosiglitazone and heart attack and did not contribute any significant new information. Data from the other two studies referenced by the committee were submitted to the FDA in 1999 and are also publicly available on its Clinical Study Register. It adds: "Cherry-picking a handful of documents from more than 14 million pages of documents distorts the record and is misleading" [5].

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