Research News

FDA Approves Tysabri®

The United States Food and Drug Administration (FDA) has approved Tysabri® (natalizumab), formerly known as Antegren®, for the treatment of relapsing-remitting forms of multiple sclerosis (RRMS). This approval was officially announced on November 23, 2004 and represents the sixth drug now approved for long-term treatment of MS. The other five are Betaseron® (interferon beta-1b), Avonex® (interferon beta-1a), Copaxone® (glatiramer acetate), Rebif® (interferon beta-1a), and Novantrone® (mitoxantrone).

Marketed by Biogen Idec and Elan Corporation, Tysabri is the first humanized monoclonal antibody to be approved for the treatment of MS. It works by inhibiting the action of adhesion molecules on the surface of immune cells, and is thought to prevent damaging immune cells from crossing the blood-brain barrier from the bloodstream and entering the brain and spinal cord. Tysabri is administered via intravenous infusions every four weeks by a medical professional.

The FDA granted accelerated approval for Tysabri based on one-year data from its two ongoing, two-year phase III trials. Previously, drugs for MS were approved only after two years of phase III trials were complete. The one-year data for Tysabri showed a 66 percent reduction in relapses compared to those on placebo (in the AFFIRM monotherapy trial) and a 54 percent relative reduction in relapses for those taking Tysabri in combination with Avonex, as compared with those taking Avonex plus placebo (in the SENTINEL add-on trial). The FDA requested that the name be changed from Antegren because another drug on the market has a similar name.

Biogen Idec and Elan report that antibodies were detected in approximately 10 percent of participants taking Tysabri at least once during treatment; six percent of participants developed antibodies that remained persistently positive. Persistently positive antibodies were associated with a substantial decrease in efficacy and an increase in certain infusion-related adverse events. Common side effects included headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, joint pain, and abdominal discomfort. The most frequently reported serious adverse reaction was infection (2.1 percent in the treatment group versus 1.3 percent in the placebo group) and included pneumonia. Tysabri had a less than one percent risk of serious allergic reactions in this study.

According to MSAA Vice President and Chief Medical Officer Jack Burks, MD, "The FDA approval of Tysabri creates excitement and caution. Excitement stems from the availability of a new class of therapy for MS. Tysabri, a monoclonal antibody, reduced the relapse rate by 66 percent over placebo and 54 percent over Avonex alone in a separate trial, when Tysabri was added to Avonex treatment. The MRI data also favors Tysabri."

Dr. Burks notes that caution is advised because:

• Tysabri is not a cure. Some patients still had attacks and ongoing MRI damage while being treated with Tysabri
• The ongoing study only has one-year data on effectiveness
• Data on the effects that Tysabri may have on disability progression will not be available until later in 2005
• While Tysabri appears stronger than Avonex, it has not been compared to other currently available MS treatments (Betaseron, Copaxone, Rebif or Novantrone)
• Longer-term safety data is important

Dr. Burks goes on to say, "In summary, we welcome this new unique MS therapy with excellent one-year data on relapses, MRI, and safety. Where it 'fits' with other MS treatments is not known. These trials cannot be directly compared to clinical trial results using other MS treatments, because the patients in the current trial had milder disease, which tends to respond better to any treatment.

"The other therapies also have FDA approval plus more than 10 years of safety and efficacy data. Additionally, four of the five drugs are self administered. Will Tysabri be a 'stand alone' treatment or will patients benefit more if it is added to their current therapies? As usual, more questions are generated by each successful clinical trial. The great news is that we have another treatment option for MS patients and we are learning more about the disease."

Please note that the information given in this or any of MSAA's publications should not be used to determine one's course of treatment. Any changes to medications or other treatments should only be done under the guidance of a medical professional.