Stopping Gilenya May Worsen Multiple Sclerosis, FDA Warns

Federal health officials are warning about potential side effects the multiple sclerosis (MS) drug Gilenya, which may cause a worsening of symptoms and disability after the drug is stopped. 

In a Drug Safety Communication issued on November 20, the FDA indicates that stopping Gilenya treatment could result in multiple sclerosis problems and symptoms that are worse than before they started taking the drug, potentially resulting in permanent disability.

Gilenya (fingolimod) was introduced by Novartis for treatment of multiple sclerosis in 2010, and it is widely used to reduce flare-ups and delay the onset of physical disability caused by the disease. An estimated 70,000 people throughout the world currently using Gilenya, which is one of several medications approved to treat a form of the disease known as relapsing MS. This includes periods of time when MS symptoms get worse.

The FDA now says it will require new label warnings about the risks associated with stopping Gilenya, which may leave individuals with worse problems than when they started taking it.

Some patients may need to stop Gilenya if they experience particular side effects, become pregnant, or if the medication isn’t working. However, even in those cases, individuals can experience worse symptoms after Gilenya is discontinued. In rare cases, stopping treatment with the drug may result in severe disability that could become permanent.

Since the drug was approved in 2010, there have been at least 35 cases of severely increased disability accompanied by multiple new lesions seen on MRI that occurred 2 to 24 weeks after Gilenya was stopped, the FDA warns. The disabilities were more severe than with typical MS relapses, and appeared to be unrelated to the patient’s prior disease state.

The warning indicates most patients experienced worsening symptoms in the first 12 weeks after stopping Gilenya. Symptoms varied and included new or worsened weakness, increased trouble using arms or legs, or changes in thinking, eyesight, or balance.

Some patients who were able to walk before stopping Gilenya then required wheel chairs or became bed bound after stopping the drug. A total of 17 patients had partial recovery, eight experienced permanent disability or no recovery, and six returned to the level of disability before or during Gilenya.

The agency’s warning is only based off of those cases submitted to the FDA’s adverse event reporting system. There may be additional cases of which the FDA is unaware. Some health experts estimate that only about 10% of all adverse drug side effects are reported to the agency.

Gilenya Brain Infection Concerns

Gilenya is already a blockbuster drug for Novartis, generating around $2.5 billion in annual sales in 2015. However, it has been linked to a potential risk of a rare but deadly brain infection, and questions have been raised about whether the drug was approved too fast, with too little research.

Several reports of Progressive multifocal leukoencephalopathy (PML) have been linked to Gilenya, which is an aggressive brain disease that damages the myelin, or fatty tissue covering the brain, which is needed for proper nerve function in the white matter.

PML brain infections have been linked to a number of similar medications, and is believed to be caused by the John Cunningham (JC) virus, which is usually a harmless virus, but can cause the serious brain infection among people who have a weakened immune system.

In August 2015, the FDA required new warnings about the link between Gilenya and progressive multifocal leukoencephalopathy (PML), indicating that patients and medical providers should be aware of potential symptoms, which may include mood changes, confusion, memory loss, weakness on one side of the body and problems walking.

According to a report published by the Journal of the American Medical Association (JAMA) in 2014, 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.

In it’s latest warning, the FDA recommends doctors inform patients of the risks before starting or stopping Gilenya treatment. When the drug is stopped, patients should be carefully observed to see if their condition deteriorates.

The agency advises patients not to stop taking the medication without consulting with their doctor first. If a patient experiences new or worsened symptoms of MS after stopping the drug, they should see a doctor immediately.

Adverse events regarding Gilenya should be reported to the FDA’s MedWatch Program immediately.