Letter Urging Rejection of Sertindole (Serdolect)

April 9, 2009

Thomas Laughren, M.D.
Director, Division of Psychiatry Products
Food and Drug Administration / CDER
10903 New Hampshire Ave
WO Building 22, Room 4114
Silver Spring, MD 20993

Dear Dr. Laughren,

On April 7, 2009, the Psychopharmacologic Drugs Advisory Committee met to discuss the use of sertindole in schizophrenia. Because of evidence from a large randomized controlled trial of an increase in risk of sudden cardiac death, the committee voted that sertindole is unsafe for broad use in schizophrenia. However, the committee voted that sertindole is “acceptably safe” for use in some patients with schizophrenia, suggesting that it might be used in patients who do not respond to or do not tolerate other therapies. Because there are safer approved therapies for schizophrenia, and because sertindole is not more effective than any of these other drugs, we believe that the risk of sudden cardiac death is unacceptable and this drug should not be approved.

Although sertindole had not been approved by the FDA, marketing in Europe was approved in 1996. It was then suspended in 1999 because of case reports of sudden cardiac death related to this drug, which was already known to cause prolongation of the QT interval, an important surrogate marker for ventricular arrhythmias and sudden cardiac death. The Sertindole Cohort Prospective (SCoP) Study was conducted to measure the risk of sudden cardiac death in patients with schizophrenia by randomizing nearly 10,000 patients to either sertindole or risperidone. The pre-specified primary endpoint of all-cause mortality was not significantly different with these two drugs, but the study failed to exclude a 50% increase in mortality with sertindole using conventional 95% confidence intervals. Much more worrisome, sertindole was associated with a fivefold greater risk of sudden cardiac death than risperidone (hazard ratio 5.1, 95% confidence interval 1.5-17.9). It is notable that the comparator drug risperidone is already thought to confer an increased risk of sudden cardiac death, based on a recently published retrospective cohort study of atypical antipsychotic use (N Engl J Med 2009;360:225-35).

The increased risk of sudden cardiac death with sertindole presents a significant public health danger, and it is hard to justify tolerating this risk when this drug is no more effective than other approved therapies for schizophrenia. Therefore, we urge the FDA not to approve this drug.

Sincerely,

James Floyd, M.D.
Researcher, Public Citizen  

Sidney Wolfe, M.D.
Acting President, Public Citizen

cc: Robert Temple, M.D., Janet Woodcock, M.D., Joshua Sharfstein, M.D.