Ofatumumab: State of the art in 2024 – Where are we now and where are we going

Česká verzia

Authors: M. Vališ ^1,2; S. Halúsková ^3,4
Authors place of work: Research Institute for Biomedical, Science – Výzkumný ústav biomedicínských, věd, z. ú., Hradec Králové ¹; International Clinical Research Center, FN U sv. Anny v Brně ²; Neurologická klinika FZS Univerzity, Pardubice a Nemocnice Pardubického, kraje, Pardubice ³; Lékařská fakulta UK v Hradci Králové ⁴
Published in the journal: Cesk Slov Neurol N 2024; 87(5): 313-316
Category: Review Article
doi: https://doi.org/10.48095/cccsnn2024313

Summary

Ofatumumab represents the first fully human anti-CD20 monoclonal antibody, developed for subcutaneous self-administration once a month. It is indicated for the treatment of active relapsing-remitting multiple sclerosis (RR-MS) and can be used as a first-line therapy in patients with negative prognostic factors suggestive of an unfavorable disease course. Ofatumumab demonstrated clear superiority over teriflunomide in registration clinical trials and long-term data from open-label extension studies which confirmed its sustained efficacy, favorable safety profile, and also a high level of patient compliance. From the patient‘s point of view, it is an attractive treatment option with a high-efficacy drug that is easy to administer via subcutaneous injection at home, requiring no premedication. Ofatumumab meets the requirements of modern pharmacotherapy and is one of the breakthrough drugs that can significantly improve the prognosis of patients with RR-MS.

Keywords:

compliance – Safety – Multiple sclerosis – ofatumumab – high effi cacy therapy – effi cacy

Zdroje

1. Novartis Kesimpta® six-year efficacy data show substantial benefits in recently diagnosed treatment-naïve people with relapsing multiple sclerosis. 2024. Dostupné z: https: //www.novartis.com/news/media-releases/novartis-kesimpta-six-year-efficacy-data-show-substantial-benefits-recently-diagnosed-treatment-naive-people-relapsing-multiple-sclerosis.

2. Hauser SL, Kappos L, Bar-Or A et al. 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. doi: 10.1007/s40120-023-00518-0.

3. Klein C, Lammens A, Schäfer W et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs 2013; 5 (1): 22–33. doi: 10.4161/mabs.22771.

4. Bar-Or A, O‘Brien SM, Sweeney ML et al. Clinical perspectives on the molecular and pharmacological attributes of anti-CD20 therapies for multiple sclerosis. CNS Drugs 2021; 35 (9): 985–997. doi: 10.1007/s40263-021-00843-8.

5. Richter WF, Bhansali SG, Morris ME. Mechanistic determinants of biotherapeutics absorption following SC administration. AAPS J 2012; 14 (3): 559–570. doi: 10.1208/s12248-012-9367-0.

6. Torres JB, Roodselaar J, Sealey M et al. Distribution and efficacy of ofatumumab and ocrelizumab in humanized CD20 mice following subcutaneous or intravenous administration. Front Immunol 2022; 13: 814064. doi: 10.3389/fimmu.2022.814064.

7. Hauser SL, Bar-Or A, Cohen JA et al.; ASCLEPIOS I and ASCLEPIOS II Trial Groups. Ofatumumab versus Teriflunomide in multiple sclerosis. N Engl J Med 2020; 383 (6): 546–557. doi: 10.1056/NEJMoa1917246.

8. Kardas P, Lewek P, Matyjaszczyk M. Determinants of patient adherence: a review of systematic reviews. Front Pharmacol 2013; 4: 91. doi: 10.3389/fphar.2013.00091.

9. Lizán L, Comellas M, Paz S et al. Treatment adherence and other patient-reported outcomes as cost determinants in multiple sclerosis: a review of the literature. Patient Prefer Adherence 2014; 8: 1653–1664. doi: 10.2147/PPA.S67253.

10. Fox E, Mayer L, Aungst A et al. Adherence and compliance with subcutaneous administration of ofatumumab in relapsing multiple sclerosis. Neurology 2021; 96 (15_supplement): 4521.

11. Alvarez E, Hersh CM, Robertson D et al. Compliance and persistence with ofatumumab treatment in patients with relapsing multiple sclerosis in clinical trials for up to 4 years. Neurology 2023; 100 (17_supplement_2): 3169. doi: 10.1212/WNL.0000000000203074.

12. Gorritz M, Chen C, Tuly R et al. Real-world persistence and adherence of ofatumumab versus platform self-injectable disease modifying therapies in patients with multiple sclerosis. Presented at the Consortium of Multiple Sclerosis Centers Annual Meeting, Aurora, CO, USA, 31 May–3 June, 2023.

13. Gorritz M, Chen C, Tuly R et al. Real-world persistence of ofatumumab vs. oral disease modifying therapies in patients with multiple sclerosis. Presented at the Consoritum of Multiple Sclerosis Centers Annual Meeting, Aurora, CO, USA, 31 May–3 June, 2023.

14. Sorensen PS, Lisby S, Grove R et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology 2014; 82 (7): 573–581. doi: 10.1212/WNL.0000000000000125.

15. Bar-Or A, Grove RA, Austin DJ et al. Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: the MIRROR study. Neurology 2018; 90 (20): e1805–e1814. doi: 10.1212/WNL.00000000000 05516.

16. Bar-Or A, Wiendl H, Montalban X et al. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study. Mult Scler 2022; 28 (6): 910–924. doi: 10.1177/13524585211044479.

17. Kira JI, Nakahara J, Sazonov DV et al. Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: phase 2 APOLITOS study. Mult Scler 2022; 28 (8): 1229–1238. doi: 10.1177/13524585211055934.

18. Hauser SL, Cross AH, Winthrop K et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler 2022; 28 (10): 1576–1590. doi: 10.1177/13524585221079731.

19. Kramer J, Linker R, Paling D et al. Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis. Mult Scler J Exp Transl Clin 2023; 9 (4): 20552173231203816. doi: 10.1177/20552173231203816.

20. El Mahdaoui S, Romme Christensen J, Magyari M et al. Intravenous ofatumumab treatment of multiple sclerosis and related disorders: an observational study. Mult Scler Relat Disord 2022; 68: 104246. doi: 10.1016/j.msard.2022.104246.

21. Hauser SL, Zielman R, Das Gupta A et al. Efficacy and safety of four-year ofatumumab treatment in relapsing multiple sclerosis: The ALITHIOS open-label extension. Mult Scler 2023; 29 (11–12): 1452–1464. doi: 10.1177/13524585231195346.

22. Du FH, Mills EA, Mao-Draayer Y. Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment. Auto Immun Highlights 2017; 8 (1): 12. doi: 10.1007/s13317-017-0100-y.

23. Ross AP, Besser C, Naval S et al. Patient and nurse preference for Sensoready autoinjector pen versus other autoinjectors in multiple sclerosis: results from a pilot multicenter survey. BMC Neurol 2023; 23 (1): 85. doi: 10.1186/s12883-023-03100-1.

24. Terlizzi RD, King M, Blohm C. Usability validation of the Sensoready® pen in patients with relapsing multiple sclerosis. Ther Deliv 2023; 14 (4): 259–268. doi: 10.4155/tde-2023-0022.

25. Cohen J, Hauser S, Zielman R et al. Effect of longer--term ofatumumab treatment on disability progression and brain volume change. Neurology 2023; 100 (17_supplement_2): 2421. doi: 10.1212/WNL.0000000000202543.

26. Pardo G, Hauser S, Bar-Or A et al. Longer-term (up to 6 years) efficacy of ofatumumab in people with recently diagnosed and treatment-naive relapsing multiple sclerosis. Neurology 2024; 102 (17_supplement_1). doi: 10.1212/WNL.0000000000206274.

27. Lublin FD, Häring DA, Ganjgahi H et al. How patients with multiple sclerosis acquire disability. Brain 2022; 145 (9): 3147–3161. doi: 10.1093/brain/awac016.

28. Harding K, Williams O, Willis M et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol 2019; 76 (5): 536–541. doi: 10.1001/jamaneurol.2018.4905.

29. He A, Merkel B, Brown JWL et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol 2020; 19 (4): 307–316. doi: 10.1016/S1474-4422 (20) 30067-3.

30. Iaffaldano P, Lucisano G, Caputo F et al. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies. Ther Adv Neurol Disord 2021; 14: 17562864211019574. doi: 10.1177/17562864211019574.

31. Hrnciarova T, Drahota J, Spelman T et al. Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries. Mult Scler Relat Disord 2023; 76: 104803. doi: 10.1016/ j.msard.2023.104803.

32. Spelman T, Magyari M, Piehl F et al. Treatment escalation vs immediate initiation of highly effective treatment for patients with relapsing-remitting multiple sclerosis: data from 2 different national strategies. JAMA Neurology 2021; 78 (10): 1197–1204. doi: 10.1001/jamaneurol.2021.2738.

33. Brown J, Coles A, Horakova D et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA 2019; 321 (2): 175–187. doi: 10.1001/jama.2018.20588.

34. Schriefer D, Haase R, Ness NH et al. Cost of illness in multiple sclerosis by disease characteristics – a review of reviews. Expert Rev Pharmacoecon Outcomes Res 2022; 22 (2): 177–195. doi: 10.1080/14737167.2022.1987218.

35. Koeditz D, Frensch J, Bierbaum M et al. Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: a cost-consequence analysis from a societal perspective in Germany. Mult Scler J Exp Transl Clin 2022; 8 (1): 20552173221085741. doi: 10.1177/20552173221085741.