Reactions 1290 - 27 Feb 2010

Rosiglitazone: accusations overcardiovascular safety

After conducting a 2-year enquiry into Avandia[rosiglitazone], the US Senate Committee on Financehas accused GlaxoSmithKline (GSK) of covering upsafety concerns, and has accused the US FDA ofoverlooking or overriding safety concerns to do with thediabetes drug.1

In a public letter to the FDA, the Committee statedthat "the totality of evidence suggests that GSK wasaware of the possible cardiac risks associated withAvandia years before such evidence became public", andaccused GSK executives of intimidating independentphysicians.1 The Committee also has demanded anexplanation from the FDA as to why the TIDE* trial wasallowed to continue after the FDA calculated thatAvandia had caused ≈ 83 000 excess heart attacksbetween 1999 and 2007 and officials had described thetrial as "unethical and exploitative". FDA officials werealso quoted as stating that there was ‘strong evidence’that rosiglitazone conferred an increased risk of heartattacks, and that the "safety of the [TIDE] study itselfcannot be assured, and is not acceptable".

GSK reject conclusionsIn response to the accusations, GSK has hit back with

a public announcement that the US Senate Committeeon Finance’s conclusions are "based on analyses that arenot consistent with the rigorous scientific evidencesupporting the safety of the drug".2 GSK has alsoaccused the Committee of cherry-picking informationfrom documents, and thus mischaracterising GSK’sefforts to research and communicate safety informationrelated to Avandia. The RECORD** study was alsoreferenced to back claims that rosiglitazone was notassociated with an overall increase in cardiovascularhospitalisation or death compared with metformin andsulfonylureas.

On a related note, the FDA has announced that it isreviewing data from the RECORD trial, which was citedas only finding an increase in heart failure, rather thancardiovascular death or hospitalisations, associated withrosiglitazone.3 The increase in heart failure inconnection with this drug is well known and stated onthe drug label. The FDA has also reminded the publicthat it communicated the possible association betweencardiovascular risk and rosiglitazone back in 2007. TheFDA have been given until 4 March 2010 to formallyrespond to the US Senate Committee on Finance.1

* TIDE: Thiazolidinedione Intervention With Vitamin D Evaluation** RECORD: Rosiglitazone Evaluated for CardiovascularOutcomes and Regulation of Glycemia in Diabetes

See also Reactions 1165 p3;801069840 and 1179p5;809082474

1. United States Senate Committee on Finance. Baucus, Grassley Release FinanceCommittee Report on Diabetes Drug Avandia, Express Concern About FDA’sRole in Protecting Patients in Ongoing Avandia Study. Media Release : 20 Feb2010. Available from: URL: http://finance.senate.gov.

2. GlaxoSmithKline. GSK rejects conclusions of Senate Committee on FinanceStaff Report on Avandia. Media Release : 20 Feb 2010. Available from: URL:http://www.gsk.com.

3. FDA Food and Drug Administration. FDA Drug Safety Communication:ongoing review of Avandia (rosiglitazone) and cardiovascular safety. InternetDocument : [2 pages], 22 Feb 2010. Available from: URL: http://www.fda.gov.

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Reactions 27 Feb 2010 No. 12900114-9954/10/1290-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved