Ublituximab-xiiy as a treatment option for relapsing multiple sclerosis

ABSTRACT

Introduction

B cell depletion has been established as an efficacious anti-inflammatory therapy in people with relapsing forms of multiple sclerosis (MS). Ublituximab (ublituximab-xiiy) is the latest approved chimeric glycoengineered anti-CD20 monoclonal antibody (mAb) for the treatment of relapsing forms of MS.

Areas covered

In this narrative review, the authors explore the safety and effectiveness of data derived from the Phase 2 and Phase 3 ublituximab trials and from their respective post-hoc analyses. Moreover, they consider the similarities and differences between the currently available anti-CD20 antibodies for treatment of relapsing MS. Lastly, the authors discuss the role and place of ublituximab in the current disease modifying therapy landscape.

Expert opinion

Ublituximab is a rapid-acting and effective anti-inflammatory option as a treatment in people with relapsing MS that significantly reduced the annualized relapse rate and MRI-based disease activity. When compared to the Phase III trials of the other two anti-CD20 mAbs (ocrelizumab and ofatumumab), ublituximab did not result with reduction of 3 or 6-month confirmed disability progression. These differences may be attributed to the overall low rate of progression in both the ublituximab and the active comparator teriflunomide arm. Future data from open-label extensions are warranted. There was no significant reduction of ublituximab on whole-brain atrophy compared to teriflunomide.

KEYWORDS:

• Ublituximab
• multiple sclerosis
• anti-CD20
• monoclonal antibodies
• relapsing MS

Article highlights

• Ublituximab is a chimeric glycoengineered anti-CD20 monoclonal antibody that induces rapid B cell depletion.

• The low fucose content within the ublituximab antibody allows significant enhancement of the antibody-dependent cellular toxicity (ADCC).

• The ULTIMATE I and ULTIMATE II Phase 3 trials demonstrated that treatment with ublituximab was safe and resulted in a significant decrease in annualized relapse rate and MRI-based activity when compared to teriflunomide in relapsing forms of multiple sclerosis (MS).

• Ublituximab did not demonstrate superiority in decreasing the 3 and 6-month confirmed disability progression and did not result with significant reduction in whole-brain atrophy when compared to teriflunomide.

• The ULTIMATE I and II trials had an overall low rate of within-trial disease activity seen in both the ublituximab and the comparator teriflunomide arms.

• Future post-hoc analyses, open-label extensions, and post-marketing studies should determine the comparative effectiveness of ublituximab when compared to the remaining disease modifying therapies (DMT) in MS.

Declaration of interest

D Jakimovski has received honoraria for serving on an advisory board for AstraZeneca. He also serves as an Associate Editor for Clinical Neurology and Neurosurgery and compensated by Elsevier B.V. R Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Keystone Heart, Protembis and Novartis for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Keystone Heart, Protembis, and V-WAVE Medical. B Weinstock-Guttman has received honoraria for serving on advisory boards and educational programs from Biogen Idec, Novartis, Genentech, Genzyme and Sanofi, Janssen, AbbVie, and Bayer. She also received support for research activities from the National Institutes of Health, National Multiple Sclerosis Society, Department of Defense, Biogen Idec, Novartis, Genentech, Genzyme, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.