June 25, 2014

Case of PML reported in European patient treated with Gilenya

Canadian pharmaceutical company Novartis has been recently informed of a report of PML (progressive multifocal leukoencephalopathy) in an individual in Europe who had received Gilenya* (fingolimod) for the treatment of multiple sclerosis (MS).

Novartis is working with the reporting physician to further understand all possible contributing factors including those beyond treatment. The course of the underlying neurological disease was rapid with unusual clinical and MRI features. The individual was treated with Gilenya for 7 months and was initiated after she received one month of treatment with interferon and azathioprine - another immunosuppressive drug ed to treat autoimmune diseases. She also received multiple courses of high dose corticosteroids before and during treatment with Gilenya.

About Gilenya

Gilenya was approved by Health Canada in 2011 as the first oral disease-modifying therapy for MS. Gilenya is generally prescribed to individuals who have tried one or more MS therapies, but are unresponsive or intolerant to them. It is also indicated for use as a monotherapy for the treatment of people with relapsing-remitting MS to reduce frequency of relapses and delay progression of disability. Approval of Gilenya was based on data from two large-scale clinical trials involving over 1,200 participants.

Gilenya is an oral capsule taken once a day. It is believed to act by retaining white blood cells in the lymph nodes, preventing entry of these cells into the central nervous system where they would promote inflammatory damage to nerves.

Learn more about Gilenya here.

About progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare, generally fatal brain disease caused by the JC virus. It is primarily associated with severely suppressed immune systems. Symptoms of PML can include: progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, changes in thinking, memory and orientation, confusion and personality changes.

Three cases of PML were previously reported in clinical trials for the MS therapy Tysabri. There were two deaths: one in a person with MS was who also taking Avonex, and one in a person with Crohn’s disease who was also taking immunosuppressants. Since Health Canada approved the use of Tysabri for MS in 2006, there have been additional cases of PML reported, including deaths.

One case of PML was reported in 2012 in an individual outside of Canada who was taking Gilenya. According to Novartis, the case of PML was likely associated to previous treatment with Tysabri. However, they did not rule out Gilenya as a contributor to the development of PML. Aside from this, there have been no cases of PML directly attributed to Gilenya in 71,000 treated individuals thus far.

Learn more about PML here.

Details of the case

The following key medical details have been sent to Novartis based on the data currently available:

  • 46 year old female from Eastern Europe experienced right sided weakness. MRI showed few small brain lesions and a large inflammatory lesion in the spinal cord. The presence of oligoclonal bands was tested in the CSF and resulted negative. A JC virus test was negative. The patient fully recovered after high dose corticosteroids. A diagnosis of MS was made in May 2012
  • In August 2012, a similar episode occurred and, by September, the patient required walking aids despite repeated continued treatment with corticosteroids. MRI continued to show brain and spinal cord lesions
  • In October 2012, treatment with interferon-beta 1a and azathioprine were initiated but discontinued after one month due to lack of response. A repeat JC virus test was negative. No information is available regarding whether the patient had JC virus antibodies
  • In November 2012, treatment with Gilenya was initiated. However, the patient continued to worsen ; weakness developed progressively and she began using bilateral walking aids
  • From April - June 2013, further worsening was reported with visual disturbances, speech impediment, memory impairment, confusion, and increasing paralysis. The patient received repeated cycles of high dose corticosteroids approximately every month with limited clinical response
  • Gilenya was discontinued on June 20, 2013. The patient was assessed for bone marrow transplantation at another medical centre. There, she showed signs of paralysis and disorientation; inflammation of the brain was suspected and high dose corticosteroids were administered. During the most recent evaluation, MRI showed large brain lesions with extensive tissue damage. A new JC virus test was conducted and tested positive.


Due to the rare and complex nature of this case, the neurologist has started extensive work-up to rule out other suspected diagnoses including Neuromyelitis Optica (NMO). MRI images have been sent to the Medical Image Analysis Centre in Basel, Switzerland for further review. The MS Society of Canada will report on any new information on this case as it becomes available.

Update: According to a statement from Novartis, this individual’s underlying disease was an aggressive form of Neuromyelitis Optica spectrum disorder (NMS) and not multiple sclerosis.

*Gilenya is a registered trademark of Novartis