Tysabri® (natalizumab)

Parent company: Biogen Idec and Elan Pharmaceuticals, Inc.

• Administered via intravenous infusion every four weeks. Dose is 300 mg.
  
  
• Approved for all individuals with relapsing types of MS. This drug is generally recommended for patients who have not responded adequately to, or who cannot tolerate, another treatment for MS.
  
  
• This laboratory-produced monoclonal antibody acts against a molecule involved in the activation and function of lymphocytes (immune-system cells produced to fight infection and disease) and their migration into the central nervous system (CNS). Recent data suggest that it may also enhance remyelination and stabilize damage to the myelin sheath (the protective covering of the nerves). Preliminary results suggest that the drug may actually produce an improvement in function.
  
  
• At 18 months and up to 24 months of treatment with Tysabri, 87 percent of RRMS patients previously treated with other disease-modifying therapies showed stable or improved MRI scans. In this same group, disability scores as measured by the EDSS were stable or improved in 59 percent of patients.

Study Information:

• The Phase III SURPASS trial continues to evaluate 1,800 individuals with RRMS who have been treated earlier with either Rebif or Copaxone, and are then switched to Tysabri after continuing to experience relapses. The study began in February 2010 and is scheduled for completion in May 2013. The primary
  
  
• outcome measure is the annualized relapse rate. A small Phase II clinical trial, Natalizumab Treatment of Progressive Multiple Sclerosis (NAPMS), is continuing at Copenhagen University Hospital to study the safety and efficacy of Tysabri treatment of PPMS and secondary-progressive MS (SPMS). It enrolled 24 patients and is scheduled for completion in January 2012.
  
  
• A small study of 20 individuals with RRMS is evaluating the role of Tysabri on cognition and neurodegeneration (the breakdown or cell death of nerve cells). Its objective is to further establish the role of Tysabri in preventing neurodegeneration in MS and to establish new markers for such damage.
  
  
• A small Phase IV study of 20 individuals who have been treated with Tysabri for 12 months, is gradually switching Tysabri treatment to Betaseron and comparing it to continuing treatment with Tysabri. The primary outcome measure is the time to a first relapse during the study; other measures include clinical and MRI findings, as well as patient-reported outcomes on quality of life and fatigue. Safety will be assessed by reports of adverse events.
  
  
• Other studies are exploring the effects of Tysabri on ambulation (walking and mobility), cognition, fatigue, depression, bladder function, sexual function, disability, and health-related quality of life. One study indicated that Tysabri-treated patients had fewer MS-related hospitalizations and emergency-room visits over one year of treatment, suggesting that it may reduce the economic burden of MS.

Progressive Multifocal Leukoencephalopathy

• Following a suspension of the drug in 2005 after two patients developed Progressive Multifocal Leukoencephalopathy (PML), an often-fatal viral infection of the brain, Tysabri was re-released in 2006.While often fatal, when discovered early in patients taking Tysabri, new treatments have helped many to survive this infection by removing Tysabri from the blood system. Severe disability is still a major concern. All patients now receive the drug through safety monitoring programs.
  
  
• As of September 2011, there were 150 reported cases of PML with Tysabri, and its labeling has been updated to further quantify the risk. The new labeling also notes the increased risk from previous use of immunosuppressive medications.
  
  
• The three major risk factors for developing PML are: being on the drug for more than two years; prior immunosuppressant therapy; and positive blood tests for previous infection with the JC virus, which causes PML.
  
  
• It is presumed that patients with no antibodies to the JC virus will be at a much-reduced risk of developing PML. A new assay (a test used for analysis) has been developed to identify antibody-negative patients. This JC virus antibody blood test is now commercially available and is under review by the FDA.
  
  
• The JCV Antibody Program (STRATIFY-2) began April 2010 and is scheduled to end December 2012. It will enroll 8,000 participants. This program will define the prevalence of the JCV antibody in the MS population, and potentially stratify patients into lower or higher risk for developing PML based on antibody status.