Research News: PML Risk and Updates on New Therapies

Although Rare, the Risk for PML Still Exists

PML is a potentially fatal brain infection, caused by the activation of the JC virus (JCV), which is present in approximately 55 percent of individuals with MS. The JCV remains dormant in most individuals, but may become active in people with weakened immune systems – such as those taking a strong immunosuppressant.

While the risk is very low, an individual with a weakened immune system needs to be anti-JCV antibody positive (as identified through a blood test) to potentially develop PML. However, a person who is anti-JCV antibody negative could be exposed to the virus at any time.

PML has been linked to a small percentage of individuals with MS taking Tysabri® (natalizumab). For individuals who are anti- JCV antibody positive, the risk ranges from less than 1 in 1,000 during the first year of treatment, to 1 in 500 during the second year, and increases thereafter. As of fall 2014, approximately 517 cases of PML were reported with Tysabri, while more than 130,000 people have been treated with this medication.

Other disease-modifying therapies (DMTs) for MS have not been directly linked to this rare brain infection. However, a history of different immunosuppressant medications and even the long-term use of steroids can increase someone’s risk of developing PML when taking other DMTs for MS.

To date, two cases of PML have been reported in individuals taking Tecfidera® (dimethyl fumarate), leading to a label change in late 2014 to include a warning about PML. Two cases were also reported in individuals taking Gilenya® (fingolimod), and in August 2015, a third case of PML was reported in a patient with relapsing MS who was treated with Gilenya. This individual did not have prior exposure to Tysabri treatment, but had been treated with chemotherapy and radiation treatment for a different condition in the past.

The good news is that PML is now often diagnosed at a much earlier stage of the illness, which greatly improves one’s chance of not only surviving, but also experiencing little or no disability as a result. PML is identified through magnetic resonance imaging (MRI) and sometimes people are diagnosed prior to experiencing any symptoms.

However, individuals at a higher risk of developing PML should watch for symptoms, and if any occur, report this to their doctor immediately. According to the United States Food and Drug Administration (FDA), symptoms of PML are diverse and may include progressive weakness on one side of the body, clumsiness, vision problems, confusion, and changes in thinking, personality, memory, and orientation. Please see Ask the Doctor in this issue for additional details on the JC virus and PML.

Two Medications Move toward Approval

Daclizumab high-yield process (DAC HYP) is a new therapy that has been studied in relapsing-remitting multiple sclerosis (RRMS). It is a humanized monoclonal antibody against CD25, a receptor on T cells that is thought to become activated in MS. The DECIDE study compared DAC HYP 150mg injected subcutaneously once every four weeks, to intramuscular interferon once weekly. Treatment with DAC HYP versus interferon resulted in significant reductions in: the annualized relapse rate (ARR); the proportion of patients who relapsed; the number of new/enlarging T2 lesions; and the risk of confirmed disability. In spring 2015, the FDA accepted the application for review of DAC HYP in relapsing forms of MS. If approved, this will be marketed under the brand name Zinbryta™.

In June 2015, positive Phase III trial results were announced for the experimental medication ocrelizumab, a monoclonal antibody presently being studied for the treatment of relapsing forms of MS. Study participants received either 600 mg of ocrelizumab via intravenous (IV) infusion every six months, or the approved 44-mcg dose of Rebif® (interferon beta-1a), given via subcutaneous injection three-times weekly. In the OPERA I and OPERA II studies, ocrelizumab showed significant reductions in: the annualized relapse rate (ARR); the progression of clinical disability; and the number of lesions in the brain. Parent company Genentech plans to submit this data to the FDA in early 2016.

Glatopa Approved for Relapsing Forms of MS

On April 16, 2015, the FDA approved Glatopa™ (glatiramer acetate injection) for the treatment of individuals with relapsing forms of multiple sclerosis (MS), including those who have experienced a first clinical episode and have magnetic resonance imaging (MRI) features consistent with MS. Glatopa is manufactured by Sandoz, a Novartis company, and is the 13th medication to be approved by the FDA as a long-term, diseasemodifying therapy for these forms of MS.

Glatopa is a generic version of Copaxone® (glatiramer acetate injection), which has been marketed by Teva Pharmaceuticals since its approval in the mid-1990s. This is the first generic version of a disease-modifying therapy for MS to be approved by the FDA. According to Sandoz, Glatopa is therapeutically equivalent to and substitutable for Copaxone. However, readers should note that Glatopa is only available in the once-daily 20-mg dose, whereas Copaxone also offers a three-day weekly administration of 40 mgs each. Both medications are given via subcutaneous (under the skin) self-injections.

Sandoz has a 24-hour phone line at 855-GLATOPA or (855) 452-8672. You may also visit for additional details.

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