FDA, EMA Consider Natalizumab as First Line in MS

Susan Jeffrey

January 23, 2013

Biogen Idec and Elan Corporation last week announced submissions to both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requesting updates to the label of natalizumab (Tysabri), allowing it to be considered as first-line therapy in patients with multiple sclerosis (MS) who are negative for antibodies to the JC virus (JCV) on a test also developed by the companies (STRATIFY JCV).

Although natalizumab is a highly effective treatment, shown to significantly slow progression of disability by 42% to 54% and reduce annualized relapse rates by about 68% in the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) trial, use of the drug has been limited by its association with an increased risk for progressive multifocal leukoencephalopathy (PML), an opportunistic viral brain infection that generally leads to death or severe disability.

However, JCV is required for the development of PML, the companies note in their release, and patients positive for anti-JCV antibodies are at higher risk for PML. Other risk factors for PML with natalizumab treatment include prior immunosuppressant use and longer duration of treatment; the highest risk is seen in patients with all 3 of these risk factors.

"These submissions are supported by risk stratification data and a risk algorithm that enable physicians and individual living with MS to make informed decisions when considering treatment with Tysabri," the companies' statement notes. "If approved, a first-line label will allow all appropriate anti-JCV antibody negative patients to consider Tysabri early in the course of treatment, regardless of the level of disease activity or prior treatment history."

Natalizumab is currently approved in more than 65 countries. In the United States, it is approved as a monotherapy for relapsing forms of MS, generally for patients who have had an inadequate response to, or are unable to tolerate, an alternative MS therapy. In the European Union, it is approved for highly active relapsing-remitting MS in adults who have not responded to beta interferons or who have rapidly evolving severe relapsing-remitting MS.