FDA Investigating a Case of PML With Gilenya

Susan Jeffrey


August 29, 2013

The US Food and Drug Administration (FDA) is reporting a case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis (MS) taking fingolimod (Gilenya, Novartis).

This is the first PML case reported in a patient who wasn't treated previously with natalizumab (Tysabri, Biogen Idec/Elan), a treatment that has already been associated with a higher risk for PML. Novartis reported a case of PML in April 2012 in a patient receiving fingolimod, but that patient had previously been treated for more than 3 years with natalizumab before switching to fingolimod.

"Patients should not stop taking Gilenya without first discussing any questions or concerns with their health care professionals," the FDA alert notes. "We are providing this alert while we continue to investigate the PML case, and we are working with Gilenya's manufacturer, Novartis, to obtain and review all available information about this occurrence.

"We will communicate our final conclusions and recommendations after our evaluation is complete," the alert adds.

Fingolimod was approved as the first oral agent for use in relapsing forms of MS in 2010, and the company reports that approximately 71,000 patients worldwide have been treated.

Novartis first reported this new case of PML in July.

The patient in question had been treated with fingolimod for approximately 8 months before being diagnosed with PML, the FDA notes. The patient had received interferon β-1a and azathioprine for 1 month before starting fingolimod, both stopped when fingolimod was started. In addition, the patient had received multiple courses of intravenous corticosteroids for several months before and after fingolimod treatment.

"The diagnosis was made based on clinical symptoms and the detection of JC viral DNA in the cerebrospinal fluid," the alert adds, and fingolimod treatment was stopped.

Asked to comment on the FDA announcement today, the company said in a statement that "having reviewed all available information to date, Novartis considers that several features of this case of PML make it unlikely to be attributable to Gilenya."

Expert MRI reviewers found the MRI lesions present before initiation of fingolimod to be atypical and could not exclude PML, the statement notes. "Furthermore, the patient was exposed to repeated (nearly every month) courses of corticosteroids both prior to and after initiation of Gilenya and one month exposure to azathioprine, contributing to net level of immunosuppression. Further, the patient received a relatively short seven month exposure of Gilenya."

Among over 71,000 patients who have been treated worldwide in trials and in practice, no previous case of PML has been attributable to fingolimod, the company adds. "For these reasons, Novartis believes it is unlikely that this case of PML is attributable to Gilenya."

"Patient safety is of paramount importance for Novartis and we continue to monitor all aspects of patient safety on an ongoing basis and continue to work with Health Authorities on this case."

For more information, read the patient Medication Guide or the Risk Evaluation and Mitigation Strategy (REMS).


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