Gilenya PML Brain Infection Case Results in FDA Investigation

Following a recent diagnosis of the serious and potentially life-threatening brain infection progressive multifocal leukoencephalopathy (PML) in a user of Gilenya, the FDA has issued a warning to alert the public and confirm that they are investigating the case.

In a safety communication issued August 29, the FDA indicates that a patient in Europe has been diagnosed with PML after taking Gilenya.

This is the first known case of the rare brain infection identified among a user of the multiple sclerosis (MS) drug who had not previously taken Tysabri, which is another MS drug that is already known to carry a risk of PML.

The patient began taking Gilenya to treat MS eight months before being diagnosed with PML. A prior case of the brain infection among a Gilenya user was reported last year, but that patient had previously used Tysabri, which is already subject to severe restrictions due to a risk of the infection.

Progressive multifocal leukoencephalopathy (PML) is an aggressive brain disease that is believed to be caused by the John Cunningham (JC) virus. It damages the myelin, fatty tissue covering the brain, which is needed for proper nerve function in the white matter. The JC virus is usually a harmless virus, but can cause PML in people who have a weakened immune system.

Symptoms of PML may include mood changes, confusion, memory loss, weakness on one side of the body and problems walking. In most cases, PML results in severe disability or death, and the FDA is urging patients and healthcare providers to immediately report any potential side effects of Gilenya through the agency’s MedWatch program.

Concerns About Side Effects of Gilenya

Gilenya (fingolimod) was introduced by Novartis for treatment of multiple sclerosis in 2010. It is used to reduce flare-ups and delay the onset of physical disability caused by MS, with approximately 70,000 people throughout the world currently using Gilenya.

The FDA fast-tracked approval for the drug through a program designed to allow drug-makers to quickly introduce medications that look promising, despite a lack of testing. However, serious questions have been raised about whether Gilenya and other medications approved through the expedited process were properly vetted.

According to a report published last year in the Journal of the American Medical Association (JAMA), Gilenya was cited as an example of a medication that may have been approved too fast. Researchers indicated that at least seven major safety issues were identified during Gilenya clinical trials, including heart problems, liver toxicity, increased risk of infection, reduced pulmonary function, teratogenicity, macular edema and a potentially risk of cancer. Clinical trials involving doses of 5mg and 2.5mg were halted due to safety reasons, leading the FDA to approve Gilenya at the lowest dose possible of 0.5mg.

Despite concerns over the safety of Gilenya when it was reviewed, the FDA agreed to fast-track the drug’s approval with only minimal testing because the drug was identified as a crucial medication that addressed needs that were not met by other treatments.

In May 2012, the FDA added new Gilenya warnings about the risk of heart problems after a patient died within 24 hours after taking the drug. Doctors were advised not to prescribe Gilenya to patients who have a history of heart problems or who take drugs that lower their heart rates. When the drug is given to patients with heart problems, health regulators indicated that they should be monitored by ECG before the first dose and continuously for six hours afterwards.

Amid a substantial number of adverse event reports submitted to the FDA after the Gilenya was approved, the Institute for Safe Medication Practices (ISMP) suggested that the drug should be restricted. The organization of drug safety experts indicated in April 2012 that the FDA should consider restrictions similar to those used on the MS drug Tysabri, which requires close patient monitoring for signs of PML.