FDA has decided to restrict the use of GlaxoSmithKline’s diabetes drug Avandia (rosiglitazone) to patients with type 2 diabetes who cannot control their disease on other medications. These new restrictions are in response to data that suggests an elevated risk of cardiovascular events such as heart attack and stroke in patients treated with Avandia.
“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,” comments Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.
Rosiglitazone also is available in combination with other diabetes medications—metformin under the brand name Avandamet or glimepiride under the brand name Avandaryl. It belongs to a class of drugs known as thiazolidinediones, or TZDs. It is intended to be used in conjunction with diet and exercise to improve glucose (blood sugar) control in patients with type 2 diabetes.
The FDA has asked GSK to develop a restricted-access program for Avandia under a risk evaluation and mitigation strategy (REMS). 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 drug in this class. Current users of Avandia who are benefiting from the drug will be able to continue using the medication if they choose to do so.
Patients will have to review statements describing the cardiovascular safety concerns associated with this drug and acknowledge they understand the risks. Doctors will have to attest to and document their patients' eligibility.
Also the 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 agency’s review of the RECORD study, important questions arose about potential bias in the identification of cardiovascular events.
The FDA is requiring this independent review to provide additional clarity about the findings. The FDA may take additional actions after the independent re-analysis of RECORD is completed.
In addition, the agency stopped GSK’s postmarketing clinical trial known as TIDE and rescinded all regulatory deadlines for completion of the trial. The TIDE trial was comparing Avandia to Actos and to standard diabetes drugs. On July 22, the firm halted enrollment into the trial on FDA’s request for a partial hold.