These Two PML Cases Did Not Involve The Patients Previously Using The MS Drug Tysabri, As Did The One Which FDA Reported In August 2013
UPDATE: On December 18, 2015 the Europeans Medicines Agency (EMA) announced it would add information about progressive multifocal leukoencephalopathy, or PML, to the Gilenya product information, along with information about basal cell carcinoma and other risks associated with Gilenya and other drugs that reduce the immune system's activity.
UPDATE: "Novartis AG (NVS) Reports Third Case of PML in Relapsing MS Patient Treated with Gilenya" (8/18/15, BioSpace)
On August 4, 2015 the FDA posted on its web site this Safety Alert, "Gilenya (fingolimod): Drug Safety Communication - FDA Warns About Cases of Rare Brain Infection", from which we get this basic information:
ISSUE: FDA is warning that a case of definite progressive multifocal leukoencephalopathy (PML) and a case of probable PML have been reported in patients taking Gilenya (fingolimod) for multiple sclerosis (MS). These are the first cases of PML reported in patients taking Gilenya who had not been previously treated with an immunosuppressant drug for MS or any other medical condition. As a result, information about these recent cases is being added to the drug label.
BACKGROUND: Gilenya is an immunomodulator shown to benefit patients with relapsing forms of MS. This type of MS causes attacks or relapses, which are periods of time when symptoms get worse. Immunomodulators alter the immune system to reduce inflammation. PML is a rare and serious brain infection caused by the John Cunningham (JC) virus. The JC virus is a common virus that is harmless in most people but can cause PML in some patients who have weakened immune systems, including those taking immunosuppressant drugs....
More detailed information about this emerging drug safety issue concerning Gilenya is found in this document, "FDA Drug Safety Communication: FDA warns about cases of rare brain infection with MS drug Gilenya (fingolimod) in two patients with no prior exposure to immunosuppressant drugs".
Strictly Confidential, No Obligation.
We get some general context on this matter from this Reuters news report, "FDA to revise Novartis' Gilenya label to reflect brain infection risk":
PML has long been a concern associated with the long-term use of MS drugs. Sales of Biogen Inc's Tecfidera and Tysabri had been affected by reports of the rare brain infection.
Caused by a common virus that is harmless for most, PML tends to trouble patients with weakened immune systems, including those taking immunosuppressants.
The infection causes symptoms such as vision problems, confusion, as well as changes in personality, memory and orientation - potentially culminating in severe disability or death.
Gilenya was approved in 2010 to reduce relapses and delay disability progression in patients with relapsing forms of MS.
The drug raked in sales of about $700 million in the Swiss drugmaker's latest quarter.
The FDA had said in August 2013 that it was investigating a case of PML in a patient taking Gilenya, but could not conclusively link the infection to the drug as the patient had been treated with other drugs as well.
As regards the resulting August 2015 revision to the Gilenya Prescribing Information (also known as "package insert" and "drug label"), the FDA SUPPLEMENT APPROVAL letter (8/4/15) to Novartis Pharmaceuticals Corporation sets the stage:
This supplemental application provides for addition of a new subsection to the Warnings and Precautions section of the prescribing information; the new subsection [5.3] describes the cases of progressive multifocal leukoencephalopathy (PML) and probable PML that have occurred in Gilenya-treated patients. Corresponding changes have been made to the Patient Counseling Information section and the Medication Guide with respect to PML.
Here is the August 2015 Gilenya - PML warning label change information, found at this part of the current drug label (accessed 8/6/15):
5.3 Progressive Multifocal Leukoencephalopathy:
A case of progressive multifocal leukoencephalopathy (PML) and a case of probable PML occurred in patients with MS who received GILENYA in the post marketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. One patient developed PML after taking GILENYA for approximately 2.5 years. The other patient developed probable PML after taking GILENYA for approximately 4 years. The diagnosis of probable PML was based on MRI findings and the detection of JCV DNA in the CSF in the absence of clinical signs or symptoms specific to PML. The patients had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with [Tysabri (natalizumab)], which has a known association with PML. The patients were also not taking any immunosuppressive or immunomodulatory medications concomitantly. At the first sign or symptom suggestive of PML, withhold GILENYA and perform an appropriate diagnostic evaluation. MRI signs may be apparent before clinical symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
We will continue to monitor the safety profile of Gilenya as regards PML and the other serious side effects this Novartis MS drug has been associated with in recent years.