Introduction

This report details a case study for assessing the benefit-risk of natalizumab for the treatment of relapsing remitting multiple sclerosis (RRMS) versus placebo or alternative RRMS drugs interferon 𝛽-1a and glatiramer acetate.

This drug was approved in 2004 by the FDA. In 2005 the drug was suspended because of an associated incidence of progressive multifocal leukoencephalopathy (PML), a rare neurological disorder. In 2006 it was re-introduced due to patient demand, but with strict risk minimization measures. In 2011 the inclusion of anti-JC virus antibody status as a PML risk factor was included in the label of natalizumab.

Natalizumab has been used as the issue of a rare serious side effect in an effective treatment for a serious disease made for an interesting case study. Key questions to be addressed were as follows:
  • 1.Should natalizumab be given marketing approval at the time of first registration given the evidence of PML in clinical trials?
  • 2.Should natalizumab be kept on the market given that increased episodes of PML were observed in the post-marketing setting?
The following pages provide a summary of the methodologies tested, lessons learned and key messages from the natalizumab case study team. Feel free to also download the full case study report published in May 2013 for reading offline.