Profile of Ofatumumab in the Treatment of Multiple Sclerosis: Design, Development and Place in Therapy

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2024 Dec 17

PMID 39687682

Authors

Zeinab Awada

Natasha Hameed

Asaff Harel

Affiliations

Soon will be listed here.

Abstract

Targeting B cells through monoclonal antibodies against CD20 has emerged as a highly effective strategy in managing disease activity in patients with relapsing forms of multiple sclerosis. This efficacy was initially demonstrated with rituximab and further affirmed with ocrelizumab. Ofatumumab is the first fully human IgG1 monoclonal antibody (mAb) approved for the treatment of MS. It is characterized by its convenient self-administered regimen of once-monthly subcutaneous injections. Its human antibody nature contributes to a significantly lower risk of immunogenicity compared to rituximab. Clinical trials have consistently shown its effectiveness in significantly reducing annualized relapse rates, MRI-detected lesion activity, and disability progression when compared to teriflunomide, a standard therapy for MS. Additionally, ofatumumab exhibits a manageable tolerability profile, with adverse events primarily comprising infections and injection-related reactions. This review describes ofatumumab pharmacology, core clinical trial data and clinical efficacy in addition to safety issues.

References

Hauser S, Kappos L, Bar-Or A, Wiendl H, Paling D, Williams M . The Development of Ofatumumab, a Fully Human Anti-CD20 Monoclonal Antibody for Practical Use in Relapsing Multiple Sclerosis Treatment. Neurol Ther. 2023; 12(5):1491-1515. PMC: 10444716. DOI: 10.1007/s40120-023-00518-0. View

De Seze J, Maillart E, Gueguen A, Laplaud D, Michel L, Thouvenot E . Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic. Front Immunol. 2023; 14:1004795. PMC: 10076836. DOI: 10.3389/fimmu.2023.1004795. View

Vudumula U, Patidar M, Gudala K, Karpf E, Adlard N . Evaluating the impact of early vs delayed ofatumumab initiation and estimating the long-term outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis patients in Spain. J Med Econ. 2022; 26(1):11-18. DOI: 10.1080/13696998.2022.2151270. View

Comi G, Bar-Or A, Lassmann H, Uccelli A, Hartung H, Montalban X . Role of B Cells in Multiple Sclerosis and Related Disorders. Ann Neurol. 2020; 89(1):13-23. PMC: 8007167. DOI: 10.1002/ana.25927. View

Torres J, Roodselaar J, Sealey M, Ziehn M, Bigaud M, Kneuer R . Distribution and efficacy of ofatumumab and ocrelizumab in humanized CD20 mice following subcutaneous or intravenous administration. Front Immunol. 2022; 13:814064. PMC: 9366925. DOI: 10.3389/fimmu.2022.814064. View

Kurrasch R, Brown J, Chu M, Craigen J, Overend P, Patel B . Subcutaneously administered ofatumumab in rheumatoid arthritis: a phase I/II study of safety, tolerability, pharmacokinetics, and pharmacodynamics. J Rheumatol. 2013; 40(7):1089-96. DOI: 10.3899/jrheum.121118. View

Wallin M, Culpepper W, Campbell J, Nelson L, Langer-Gould A, Marrie R . The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology. 2019; 92(10):e1029-e1040. PMC: 6442006. DOI: 10.1212/WNL.0000000000007035. View

Bellot M, Luetjens C, Bagger M, Horvath C, Sutter E, DeLise A . Effect of ofatumumab on pregnancy, parturition, and lactation in cynomolgus monkeys. Reprod Toxicol. 2021; 108:28-34. DOI: 10.1016/j.reprotox.2021.12.006. View

Klein C, Lammens A, Schafer W, Georges G, Schwaiger M, Mossner E . Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs. 2012; 5(1):22-33. PMC: 3564883. DOI: 10.4161/mabs.22771. View

10.

Klineova S, Lublin F . Clinical Course of Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018; 8(9). PMC: 6120692. DOI: 10.1101/cshperspect.a028928. View

11.

Hittle M, Culpepper W, Langer-Gould A, Marrie R, Cutter G, Kaye W . Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region. JAMA Neurol. 2023; 80(7):693-701. PMC: 10186207. DOI: 10.1001/jamaneurol.2023.1135. View

12.

Kang C, Blair H . Ofatumumab: A Review in Relapsing Forms of Multiple Sclerosis. Drugs. 2021; 82(1):55-62. PMC: 8748350. DOI: 10.1007/s40265-021-01650-7. View

13.

van Nierop G, van Luijn M, Michels S, Melief M, Janssen M, Langerak A . Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients. Acta Neuropathol. 2017; 134(3):383-401. PMC: 5563341. DOI: 10.1007/s00401-017-1744-4. View

14.

Rolfes L, Meuth S . Stable multiple sclerosis patients on anti-CD20 therapy should go on extended interval dosing-"Yes". Mult Scler. 2021; 28(5):691-693. PMC: 8978458. DOI: 10.1177/13524585211055593. View

15.

Ostergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes P . Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 2010; 62(8):2227-38. DOI: 10.1002/art.27524. View

16.

Kira J, Nakahara J, Sazonov D, Kurosawa T, Tsumiyama I, Willi R . Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study. Mult Scler. 2021; 28(8):1229-1238. DOI: 10.1177/13524585211055934. View

17.

Samjoo I, Worthington E, Drudge C, Zhao M, Cameron C, Haring D . Comparison of ofatumumab and other disease-modifying therapies for relapsing multiple sclerosis: a network meta-analysis. J Comp Eff Res. 2020; 9(18):1255-1274. DOI: 10.2217/cer-2020-0122. View

18.

Ziemssen T, Groth M, Ettle B, Bopp T . Immune Response to SARS-CoV-2 mRNA Vaccines in an Open-Label Multicenter Study in Participants with Relapsing Multiple Sclerosis Treated with Ofatumumab. Vaccines (Basel). 2022; 10(12). PMC: 9782480. DOI: 10.3390/vaccines10122167. View

19.

Kelsey A, Casinelli G, Tandon M, Sriwastava S . Breast Carcinoma After Ocrelizumab Therapy in Multiple Sclerosis Patients: A Case Series and Literature Review. J Cent Nerv Syst Dis. 2021; 13:11795735211037785. PMC: 8419566. DOI: 10.1177/11795735211037785. View

20.

Bajwa H, Novak F, Nilsson A, Nielsen C, Holm D, Ostergaard K . Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients. Mult Scler Relat Disord. 2022; 60:103729. PMC: 8898195. DOI: 10.1016/j.msard.2022.103729. View