[Cladribin. Development of an oral formulation for the treatment of multiple sclerosis]

Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system in which autoreactive CD4(+) and CD8(+) T lymphocytes, B lymphocytes, macrophages, antibodies, and cytokines attack the myelin sheaths and damage the axons. The basic therapeutic agents and disease-modifying drugs that are currently available for MS require regular and frequent parenteral administration and therefore long-term compliance is unsatisfactory. Among all of the new oral MS agents presently under development, cladribine is the only substance that appears able to achieve long treatment-free intervals after only short-term administration. Cladribine is an immunomodulator with a long-lasting effect and a well-characterized safety profile based on over 15 years of experience with the parenteral route for MS and other indications. This contribution addresses the need for novel MS treatment approaches to improve compliance and describes the mechanism of action of cladribine, the available data on effectivity and safety, and the clinical development of the oral formulation of cladribine. The results from the recently published 96-week, double-blind, randomized, placebo-controlled, multicenter study CLARITY (CLAdRIbine Tablets Treating MS OrallY) are very promising. They clearly show that oral cladribine reduces relapse rate, disability progression and disease activity and burden as evidenced by MRI.