Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

Three very promising new treatments of neuromyelitis optica spectrum disorder

As yet, there are no approved therapies for neuromyelitis optica spectrum disorder (NMOSD), but that may very likely change soon. Three monoclonal antibodies submitted promising safety and efficacy results on relapse prevention. They are inebilizumab, eculizumab, and satralizumab.

Inebilizumab was tested in the phase 3, double-masked, randomised, placebo-controlled trial N-Momentum [1]. Participants were randomised 3:1 to inebilizumab or placebo for 6.5 months. Concurrent treatment with other immune suppressants was prohibited. The primary outcome measure was time-to-first adjudicated attack after 28 weeks. The 230 subjects from 24 countries were randomised and dosed (212 seropositive for anti-AQP4 antibodies).

Inebilizumab was associated with a 77% reduction in risk of developing an NMOSD attack in AQP4-IgG seropositive patients (HR 0.227; P< 0.0001). The effect on the total population, including AQP4-IgG seronegative patients was similar: 73% reduction (HR 0.272; P< 0.0001). After 28 weeks, 89% of AQP4-IgG actively treated seropositive patients were attack-free vs 58% in the placebo group. Also, inebilizumab demonstrated statistically significant benefits in key secondary endpoints, including reduction in: worsening from baseline in Expanded Disability Status Scale (EDSS) scores (P=0.0049); NMOSD-related hospitalisations (P=0.01); and frequency of cumulative total active MRI lesions (P=0.0034). Inebilizumab demonstrated a favourable safety and tolerability profile, with an adverse event rate similar to placebo.

In a randomised, double-blind, time-to-event trial, eculizumab had a significantly lower risk of relapse than placebo among 143 patients with AQP4-IgG-positive NMOSD [2]. There was no significant between-group difference in measures of disability progression. Upper respiratory tract infections and headaches were more common in the eculizumab group.

A subgroup analysis of the the SAkuraSky study showed that satralizumab is effective in reducing relapse, especially in NMO/NMOSD AQP4-Ab-positive patients [3]. Satralizumab showed a 79% risk reduction of relapses compared to placebo in this subgroup (HR 0.21).

  1. Cree B, et al. A Double-masked, Placebo-controlled Study with Open-label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adult Subjects with Neuromyelitis Optica Spectrum Disorders–Top line efficacy and safety results. AAN 2019, Plen02.001.
  2. Pittock SJ, et al. Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 May 3. doi: 10.1056/NEJMoa1900866. [Epub ahead of print]
  3. Yamamura T, et al. Efficacy of satralizumab (SA237) in subgroups of patients in SAkuraSky: a Phase III double-blind, placebo-controlled, add-on study in patients with neuromyelitis optica spectrum disorder (NMOSD). AAN 2019, S43.008.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.