EMA and FDA Take Action on GSK's Avandia

The European Medicines Agency and the US Food and Drug Administration announced individual regulatory decisions and resulting actions regarding the marketing of GlaxoSmithKline’s (London) Avandia (rosiglitazone), a thiazolidinedione used to treat Type 2 diabetes.
 
In the European Union, EMA suspended the marketing authorization for all rosiglitazone-containing medicines (Avandia, Avandamet, and Avaglim). As a result, physicians in Europe are being advised that affected patients need to be transitioned to alternative treatment options. EMA says the suspension will remain in place unless convincing data are provided that identify a group of patients in whom the benefits of the medicine outweigh its risks.
 
In the US, all rosiglitazone-containing medicines (Avandia, Avandamet and Avandaryl) will remain available with additional safety labeling and restrictions for use. FDA will also require a Risk Evaluation and Mitigation Strategy (REMS) program with additional measures to ensure the safe use of the medicine. Under the REMS, Avandia will be available to new patients only if they are unable to achieve glucose control on other medications and are unable to take Actos (pioglitazone), the only other thiazolidinedione, on the market. Actos is marketed by Takeda Pharmaceutical (Osaka, Japan). Current users of Avandia who are benefiting from the drug will be able to continue using the medication if they choose to do so.
 
Doctors will have to attest to and document their patients' eligibility. Patients will have to review statements describing the cardiovascular safety concerns associated with this drug and acknowledge they understand the risks. The agency anticipates that the REMS will limit use of Avandia significantly, according to FDA. 
 
“Allowing Avandia to remain on the market, but under restrictions, is an appropriate response, given the significant safety concerns and the scientific uncertainty still remaining about this drug,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in the FDA statement.
 
FDA ordered GSK to convene an independent group of scientists to review key aspects of the company’s clinical trial known as RECORD, which studied the cardiovascular safety of Avandia compared to standard diabetes drugs. During the course of the FDA’s review of the RECORD study, questions arose about potential bias in the identification of cardiovascular events. FDA is requiring this independent review to provide additional clarity about the findings. FDA may take additional actions after the independent re-analysis of RECORD is completed.
 
In addition, the agency halted the GSK’s clinical trial known as TIDE and rescinded all of the regulatory deadlines for completion of the trial. The TIDE trial compares Avandia with Actos and to standard diabetes drugs. TIDE is the only GSK-sponsored clinical trial using Avandia currently being conducted in the US and Europe.  GSK, in conjunction with the TIDE-steering committee, will communicate this decision to local regulatory agencies, ethics committees, and institutional review boards, according to GSK.
 
GSK says it is working with FDA and EMA to implement the required actions and will also work closely with other regulatory agencies to comply with any decisions made by them regarding rosiglitazone-containing medicines. GSK is voluntarily ceasing promotion of Avandia in all the countries in which it operates and will continue to respond to requests for information and support from healthcare professionals and patients.   
 
Total sales of Avandia products in the first half of 2010 were £321 million ($507 million), a decline of 18%, according to GSK. US sales fell 23% to £164 million ($259 million), and European sales declined 17% to £72 million ($114 million). As a result of the regulatory updates in both the US and EU, GSK expects global sales of Avandia products to be approximately £100 million ($158 million) to £150 million ($237 million) in the second half of 2010 and with minimal annual sales thereafter.

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