Investigational drugs in development to prevent neuromyelitis optica relapses

ABSTRACT

Introduction: In the short time since 2014, three pivotal, worldwide studies in neuromyelitis optica spectrum disorders have been launched: eculizumab, SA237 and inebelizumab, each based on a unique mechanism.

Areas covered: In this review, we provide a discussion on the trial data available for each drug, a brief description of the trial design, and our expert opinion on the potential benefits and risks.

Expert opinion: Eculizumab, a C5 complement inhibitor, may prove useful in the treatment of intractable cases of NMOSD, but physicians must be aware of the known risk of meningococcal infection. SA237, an interleukin-6 receptor blocker, may be effective at reducing relapse risk, and also has the potential to reduce neuropathic pain in NMOSD. Inebelizumab, a B cell depleting agent, has never been tested in NMOSD, but based on extensive evidence of efficacy with B cell depletion using rituximab, inebelizumab is expected to work at least as well.

KEYWORDS:

• Neuromyelitis optica
• biomarkers
• prognosis
• risk assessment

Declaration of interest

F. Paul received research support from the German Ministry for Education and Research (BMBF/KKNMS; Competence Network Multiple Sclerosis), research support from the Deutsche Forschungsgemeinschaft (DFG) (grant Exc.257) and from the Guthy Jackson Charitable Foundation and National Multiple Sclerosis Society, research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. M. Levy currently receives research support from: National Institutes of Health, Maryland Technology Development Corporation, Sanofi, Genzyme, Alexion, Alnylam, Shire, Acorda and Apopharma. He also received personal compensation for consultation with Alexion, Acorda, and Genzyme and he serves on the scientific advisory boards for Alexion, Acorda and Quest Diagnostics. 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.

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

Article highlights

• Neuromyelitis optica spectrum disorders (NMOSD) are rare and oftentimes devastating autoimmune central nervous system conditions with preferential affection of the optic nerves, spinal cord and brainstem

• Given the rarity of the disease no rigorous controlled clinical trials have been performed to date

• Long-standing clinical experience and data from uncontrolled studies have shown that B cell depleting therapies such as rituximab or broad immunosuppressive medications such as prednisolone, azathioprine, or mycophenolate prevent relapses and reduce attack severity in a subset of patients

• Based on recent insights into the immunopathogenesis of NMOSD, novel treatment strategies (antibodies targeting CD19, IL6, or complement) are currently under investigation in randomized controlled trials that will hopefully lead to the approval of specific medications for attack prevention in NMOSD in the near future

Additional information

Funding

This paper was not funded.