The writing is on the wall for GlaxoSmithKline's Avandia now that the European Medicines Agency has recommended suspension of the controversial diabetes drug, while its counterpart in the USA has severely restricted its use.
The EMA has called for the suspension of the marketing authorisations for Avandia (rosiglitazone), Avandamet (rosiglitazone/metformin) and Avaglim (rosiglitazone/glimepride), noting that these medicines will stop being available in Europe within the next few months. The agency's Committee for Medicinal Products for Human Use began its latest review of the drug in July, noting that since its first authorisation in 2000, "rosiglitazone has been recognised to be associated with fluid retention and increased risk of heart failure and its cardiovascular safety has always been kept under close review".
Data from clinical trials, observational studies and meta-analyses that have become available over the last three years have "suggested a possibly increased risk of ischaemic heart disease", which led to further restrictions being put in place", the EMA said. The availability of more recent studies "has added to the knowledge about rosiglitazone" and so the CHMP has decided that its benefits no longer outweigh its risks.
The suspension will remain in place unless GSK can provide "convincing data to identify a group of patients in whom the benefits of the medicines outweigh their risks", the EMA noted, and the recommendation has now been forwarded to the European Commission for the adoption of a legally-binding decision.
On the other side of the Atlantic, the US Food and Drug Administration has decided not to recommend pulling Avandia but says it will "significantly restrict" its use to patients who cannot control their diabetes on other medications. The agency also ordered GSK to bring in an independent group of scientists to review the key RECORD study which compared the safety of Avandia to standard diabetes drugs, and halted the TIDE, which compares rosiglitazone to Takeda's Actos (pioglitazone) another drug in the same class, and other treatments.
Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, noted that "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."
As for GSK, chief medical officer Ellen Strahlman, said the company "continues to believe that Avandia is an important treatment for patients" but would work with the regulatory agencies and doctors to implement the required actions. The firm noted that it will voluntarily cease promotion of Avandia in all the countries in which it operates.
Total sales of Avandia products in the first half of 2010 were £321 million (-18%), half of which came from the USA, and they have been declining steadily over the last few years. GSK noted that global sales of the drugs will be in a range of £100-£150 million in the second half "and with minimal annual sales thereafter". Associated one-off costs, including asset write-offs are currently expected to be approximately £100 million on a pre-tax basis.