Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases
by Honghui Zhou, Diane R. Mould
18Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins in Multiple Sclerosis – Peginterferon Beta‐1a, Daclizumab Beta, Natalizumab
Xiao Hu1,2Yaming Hang1,3Lei Diao1,4 Kumar K. Muralidharan1 and Ivan Nestorov1
1Biogen, 225 Binney Street, Cambridge, MA, 02142, USA
2Wave Life Sciences, 733 Concord Ave, Cambridge, MA, 02138, USA
3Takeda Pharmaceuticals International Co., Cambridge, MA, 02138, USA
4BMS China, 15F, Wheelock Square, 1717 West Nanjing Road, Shanghai, China
18.1 Introduction
Multiple sclerosis (MS) is an autoimmune inflammatory disorder of central nervous system (CNS), characterized by demyelination and variable degrees of axonal loss, resulting lesion sites in CNS. It affects approximately 400 000 people in the United States and 2.5 million worldwide and mostly young women (between ages 20 and 40 years) [1–4]. Based on clinical presentation, MS is categorized into three forms, relapsing–remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), and primary progressive multiple sclerosis (PPMS). Both PPMS and SPMS are progressive forms of the disease and are generally more severe than RRMS. The clinical difference between PPMS and SPMS is that PPMS starts with progressive disease, while SPMS is developed from RRMS. RRMS is characterized by unpredictable relapses, followed by variable recovery and periods of clinical stability, and accounts for 80% of all MS patients. Within 10 years more than 50% of RRMS patients eventually ...