- Highly active relapsing remitting multiple sclerosis (RRMS)
Its initial licensed indication for the treatment of relapsing multiple sclerosis, was followed by a voluntary withdrawn for this indication after a 3 patients developed progressive multifocal leukoencephalopathy, 2 of which later died. One of these patients had been a participant in a parallel development programme for Crohn's Disease. It is thought that the immunosuppression from the drug may have increased the patients susceptibility to the JC virus . Use in stricter indications in multiple sclerosis has now resumed.
The FDA's early approval of drug was seen by some as premature given that cumulative safety data had not been received . The drug was introduced on the basis of relative short trial data (of only 1 year). At the time of FDA approval, neither of the 2 randomised controlled trials had been published in peer-reviewed journals, although they had been presented at international conferences and have now been subsequently published ,. However remarketing was allowed by the FDA in the middle of 2006. By 2009 14 cases of PML had occurred in treating multiple sclerosis giving a risk of about 1:1000. It was still unknown at this time if any of several postulated approaches to predicting risk of PML would actually work in clinical practice.
Natalizumab has also been used in a trial for treatment of Crohn's disease, but it is unclear whether the drug will be licensed for this indication after the side effects from the multiple sclerosis trial. Interestingly it had been rejected by the EMEA and a few days later a favorable opinion has been given by an FDA panel.
A license for use in patients with rapidly evolving severe RRMS defined by two or more disabling relapses in one year and with one or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous MRI was obtained in the EU in 2006.
- ↑ Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue EW, Jager HR, Clifford DB. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006 Mar 2;354(9):924-33.
- ↑ Chaudhuri. Lessons for clinical trials from natalizumab in multiple sclerosis. BMJ 2006
- ↑ Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910.
- ↑ Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA, Sandrock AW; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):911-23.
- ↑ Major EO. Reemergence of PML in natalizumab-treated patients--new cases, same concerns. The New England journal of medicine. 2009 Sep 10; 361(11):1041-3.(Link to article – subscription may be required.)
- ↑ Sandborn et al. Natalizumab induction and maintenance therapy for Crohn's disease. NEJM 2005
- ↑ EMA opinion
- ↑ Elan and Biogen's Tysabri gets panel backing for Crohn's. Pharmatimes accessed 1 Aug 2007