Biogen Idec Inc., maker of the popular multiple sclerosis (MS) pill dimethyl fumarate (Tecfidera), announced the death of a patient taking the drug who succumbed to complications from a rare brain infection. Executives broke the news during a conference call with analysts last Wednesday.
The brain infection known as progressive multifocal leukoencephalopathy (PML) took the life of a European patient who had been on the popular pill for more than four years. The patient was taking part in a long-term safety study of Tecfidera.
"The patient was a participant in the ongoing ENDORSE extension study," confirmed Catherine Falcetti, associate director of public affairs for Biogen, in an interview with Healthline.
“This patient was treated with Tecfidera for 4.5 years as part of the ENDORSE study,” explained Falcetti. “They developed PML and recently died due to complications associated with aspiration pneumonia.”
MS Drugs Suppress the Immune System
The majority of MS disease modifying drugs have an impact on the immune system. They suppress lymphocytes — T-cells or B-cells — to slow the disease by blocking the inflammation that is characteristic of MS.
But toying with the inner workings of the immune system can have serious consequences, one of which is lymphopenia, or low white blood cell count. While depleting these cells acts to tamp down the immune response in MS patients and bring their disease under control, it also opens the door for viral and bacterial invaders to gain the upper hand.
People who have lymphopenia don’t have enough lymphocytes on hand to fight off or prevent infections. That’s what happened in this case.
“This patient had severe, prolonged lymphopenia for 3.5+ years while on therapy. Severe, prolonged lymphopenia is a risk factor for PML. Because Tecfidera can cause lymphopenia, a contributory role of Tecfidera cannot be excluded,” said Falcetti.
What Causes PML?
Although PML is rare, those with a weakened immune system are at greater risk. Cancer patients taking chemotherapy drugs, transplant patients on anti-rejection medicines, AIDS patients, and people taking drugs for autoimmune conditions like MS all have an increased chance of getting PML. But what is the trigger?
PML is a reactivation of the John Cunningham virus (JCV), a virus that more than three-quarters of the American population carries in their bodies. Childhood infection is common, and although this virus stays with you forever, a normal immune system is capable of keeping it at bay.
When the immune system isn’t functioning normally due to illness or is suppressed by medication, however, JCV can reactivate. When this happens, PML can develop and the brain becomes infected.
“The occurrence of PML is not limited to people who have MS, and even if a person has been exposed to the virus and has taken immune-modulating therapies, it does not mean that they will develop PML,” Bruce F. Bebo Jr., Ph.D., executive vice president of research for the National Multiple Sclerosis Society (the Society), told Healthline in an interview. “So far, in people with MS, PML has occurred mostly in people who have taken natalizumab (Tysabri).”
According to the National Institute of Neurological Disorders and Stroke (NINDS), the best treatment for PML is “reversal of the immune-deficient state, since there are no effective drugs that block virus infection without toxicity.” NINDS also states that a plasma exchange will help hasten removal of the drug from the patient’s body.
The U.S. Food and Drug Administration (FDA) has given special permission to treat PML patients with several new experimental drugs that have been effective against the infection in early testing.
“The [FDA] keeps a watchful eye on adverse events that occur both during a drug’s clinical trials and after it enters the market,” said Bebo. “The National MS Society has confidence in the agency’s role, and we are following the FDA’s investigation and will provide updates if and when more information is available.”
If you have concerns about your own lymphocyte count or JCV status, speak with your doctor. They can order a complete blood count to reveal if you have lymphopenia. They may also order a free JCV antibody test known as Stratify JCV, developed by Biogen after another of their MS drugs, Tysabri, was found to put some patients at risk for PML.
As for the Society’s recommendation, “There is currently insufficient information about possible measures that a person can take to prevent PML,” Bebo said, “outside of those measures developed to reduce the risk of PML for people taking or considering taking [Tysabri].”