alemtuzumab + natalizumab

A sequential combination therapy being investigated for relapsing forms of multiple sclerosis (MS). This therapeutic approach involves administering natalizumab followed by alemtuzumab.

Natalizumab is a humanized monoclonal antibody that targets α4-integrin, blocking the interaction between α4β1 and α4β7 integrins and their counter-receptors. This prevents the transmigration of lymphocytes from the blood into the central nervous system (CNS), reducing inflammation in MS patients.

Alemtuzumab is a monoclonal antibody targeting CD52, a cell surface antigen present on T and B lymphocytes, natural killer cells, monocytes, and macrophages. It causes antibody-dependent cellular cytolysis and complement-mediated lysis, resulting in depletion of lymphocytes followed by repopulation with altered proportions of lymphocyte subsets.

The rationale behind this sequential therapy is to address two challenges: natalizumab's association with progressive multifocal leukoencephalopathy (PML) risk and disease reactivation after cessation of treatment. The SUPPRESS trial (ClinicalTrials.gov ID: NCT03135249) is investigating whether alemtuzumab administration after natalizumab can reduce disease activity in patients with relapsing MS by establishing a disease-free state.