Current and emerging biologics for the treatment of neuromyelitis optica spectrum disorders

ABSTRACT

Introduction

Treatment options for patients suffering from neuromyelitis optica spectrum disorders (NMOSD) so far have relied on off-label and empiric drugs. The first drug for the therapy of anti-aquaporin-4 (AQP4) antibody-seropositive NMOSD patients has been approved in 2019: the C5 complement inhibitor eculizumab. The interleukin-6 receptor inhibitor satralizumab and anti-CD19 antibody inebilizumab have published positive phase III trial results and await approval in the near future.

Areas covered

We sum up current treatment options and portray in detail the new developments in NMOSD drugs focusing on phase III clinical trials, followed by an overview of emerging drugs in less advanced clinical trial stages.

Expert opinion

Eculizumab’s approval by the competent authorities marks a milestone in NMOSD treatment. Satralizumab and inebilizumab will most likely follow in approval given their presented results in efficacy and safety. All three drugs have shown efficacy in reducing relapse rates in NMOSD patients with anti-AQP4 antibodies. Although we will have even more evidence-based therapy options in the future, empirically used medications will keep their importance for now. The potential effect of new medications in AQP4 antibody-seronegative NMOSD and patients with an NMOSD phenotype and antibodies to myelin oligodendrocyte glycoprotein remains to be determined.

KEYWORDS:

• NMOSD
• clinical trials
• eculizumab
• satralizumab
• inebilizumab

Article highlights

• The rare autoimmune CNS condition of neuromyelitis optica spectrum disorders (NMOSDs) typically manifests with attacks affecting the optic nerves, brainstem, and myelon and can lead to irreversible disability – consequent treatment of acute attacks and prevention of subsequent attacks are, therefore, paramount.

• A highly specific antibody to aquaporin 4, an astrocyte water channel protein in the CNS, can be detected in a high proportion of patients diagnosed with NMOSD.

• Current treatment options rely on clinical experience from off-label use of B cell-depleting and immunosuppressive drugs and small controlled trials, but the need for sufficiently powered randomized controlled trials to investigate effective treatment strategies is high.

• In NMOSD, antibodies targeting CD19 (inebilizumab), the interleukin 6 receptor (satralizumab), and the complement system (eculizumab) have been investigated in recent phase III studies, and their overall positive results in AQP4 antibody-positive NMOSD published in 2019 have so far led to a first official approval for a drug for the treatment of aquaporin 4-seropositive NMOSD: C5 inhibitor eculizumab. Approval of satralizumab and inebilizumab is expected in 2020 or 2021.

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Declaration of interest

A Duchow has received a speaker honorarium from Roche, not related to the preparation of this manuscript. J Bellmann-Strobl has received travel grants and speaking honoraria from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi Genzyme, Teva Pharmaceuticals, Roche, and Novartis, none of them related to preparing this manuscript. F Paul served on the scientific advisory boards of Novartis and MedImmune; received speaker honoraria and travel funding from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune/Viela Bio, and Shire; serves as academic editor of PLoS ONE and associate editor of Neurology: Neuroimmunology & Neuroinflammation; consulted for Sanofi-Genzyme, Biogen, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Guthy Jackson Charitable Foundation, and NMSS. 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

One of the reviewers on this manuscript has received personal fees for consulting and lectures from Alexion Pharma, personal fees for consulting from Roche, and their institution has received reimbursements for the participation in the Eculizumab PREVENT study (Alexion). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.