Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis

• DOI: 10.1111/cei.13208
• Publication Date: 2018-08-24T12:44:50Z
• Authors: Z Li; S Richards; H K Surks; A Jacobs; M A Panzara
• Keywords: CD52; Pharmacodynamics

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for treatment of relapsing multiple sclerosis (MS). In the Phase II/III trials, patients received 12 or 24 mg/day alemtuzumab in two courses (5 days course 1 and 3 2), months apart. Serum concentrations peaked on last day dosing each mostly fell below limit quantitation by 30. Alemtuzumab rapidly depleted circulating T B lymphocytes, with lowest observed values occurring within days. Lymphocytes repopulated over time, cell recovery usually complete 6 months. lymphocytes recovered more slowly generally did not return to baseline post-treatment. Approximately 40 80% had total lymphocyte counts, reaching lower normal after course, respectively. The clearance dependent count. A majority treated tested positive anti-alemtuzumab antibodies, including inhibitory during 2-year studies, higher proportion 2 than 1. presence antibody appeared be associated slower from circulation but no impact pharmacodynamics. No effects age, race gender pharmacokinetics pharmacodynamics were observed. Together, pharmacokinetics, immunogenicity results support continued development use MS, probably explain its sustained beyond interval.