Neuromyelitis Optica Spectrum Disorder (NMOSD)

Soliris® (eculizumab) is a terminal complement protein inhibitor developed and commercialized by Alexion Pharmaceuticals that is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 water channel autoantibody (AQP4-IgG)-positive.1,2 In the EU, eculizumab is also indicated for patients with relapses of the disease.1 Eculizumab is a recombinant humanized monoclonal antibody (rhuMAb) that inhibits the activation of complement system proteins and targets human complement component 5 (C5), to which it binds with high affinity.1 Soliris was initially approved by the US Food and Drug Administration (FDA) in 2007 for the treatment of paroxysmal nocturnal hemoglobinuria and myasthenia gravis. FDA approval for NMOSD was granted in 2019.3

NMOSD is a demyelinating and autoimmune disease affecting the central nervous system (CNS).1 It is a rare and life-threatening condition that may severely disable patients, as it is mainly characterized by inflammation of the optic nerve and spinal cord, causing optic neuritis and transverse myelitis, respectively. Pain inside the eye, loss of vision, and perturbation of motor, sensory, and autonomic functions are symptoms experienced by patients with NMOSD.4 Recurrent attacks or relapses of optic neuritis or myelitis are observed in these patients. Recovery from these attacks may not be complete, which can leave a residual impairment that accumulates over time. A minority of patients, however, experience a single attack or do not seem to accumulate disability over time.1

Mechanism of Action and Usage of Eculizumab

About 75% to 90% of patients with NMOSD present with IgG autoantibodies in their serum directed at the AQP4 protein. In these patients, AQP4-IgG can reach the CNS and bind to AQP4 expressed on astrocytes that are part of the blood-brain barrier (BBB).1 Binding to the AQP4 protein activates the complement cascade and consequently induces damage of CNS cells. Demyelination occurs due paranodal targeting of AQP4 near oligodendroglial loops, along with the death of neurons located in the optic nerve and spinal cord.5 

Eculizumab is a complement inhibitor that binds to the C5 complement protein in the terminal part of the complement cascade.1 Although the precise mechanism of action of eculizumab remains unclear, it is presumed that the high-affinity binding to C5 prevents C5 cleavage into C5a and C5b and the subsequent formation of the terminal complement complex C5b-9.2

Soliris is formulated in 30-mL single-dose vials as a colorless, clear, and sterile 10 mg/mL solution for intravenous (IV) use. The recommended administration of eculizumab in adults with AQP4-IgG-seropositive NMOSD is 900 mg weekly for the first 4 doses, 1200 mg for the fifth dose, and 1200 mg every 2 weeks thereafter. Soliris should be administered as an IV infusion, and patients should be monitored for at least 1 hour after completion of the infusion.2

Access the Soliris monograph page at MPR for full prescribing information.

The use of eculizumab is associated with an increase in susceptibility to opportunistic meningococcal infections, such as those caused by Neisseria meningitidis. The administration of eculizumab is therefore contraindicated in patients with unresolved serious N. meningitidis infection and who are not currently vaccinated against N. meningitidis. Meningococcal vaccination should be given at least 2 weeks before the first dose of eculizumab.2 Due to the significant risk of infection, Soliris is only available to patients through a program under a Risk Evaluation and Mitigation Strategy (REMS).2

The most frequent adverse reactions observed with the use of Soliris include upper respiratory infection, diarrhea, back pain, dizziness, joint pain, pharyngitis, flu-like symptoms, urinary tract infections, pyrexia, and bruising.2

Soliris in Clinical Trials

The efficacy of eculizumab for the treatment of NMOSD was evaluated in the phase III PREVENT study (NCT01892345). This was a randomized, double-blind, placebo-controlled study that enrolled 143 NMOSD patients with anti-AQP4 antibody positivity. Ninety-six patients were randomized to receive eculizumab and 47 patients were randomized to receive a placebo. The eculizumab-treated group received 900 mg weekly for the first 4 doses and 1200 mg every 2 weeks thereafter.6

The trial included patients who were at least 18 years of age and presented with a history of at least 2 relapses in the last 12 months or 3 relapses in the last 24 months and at least 1 relapse in the 12 months before screening. Patients were also required to have an Expanded Disability Status scale (EDSS) score of ≤7, a stable dose regimen if on immunosuppressive therapy, and a limited use of corticosteroids of ≤20 mg per day. Patients treated with rituximab or mitoxantrone in the 3 months before screening were not eligible for participation. Patients receiving IV immunoglobulin in the 3 weeks prior to screening were also excluded from the study.6

The primary endpoint in the PREVENT study was the time to the first adjudicated on-trial relapse. The results of the study revealed that for adults receiving eculizumab, the time to the first relapse was significantly longer than that in patients receiving placebo. Additionally, a 94% reduction in risk of relapse was observed in eculizumab-treated patients.6 Patients completing the PREVENT study were able to enroll in an ongoing open-label extension trial (NCT02003144) to receive a 1200 mg eculizumab maintenance dose every 2 weeks and after a 4-week blinded induction phase.


1. Frampton JE. Eculizumab: a review in neuromyelitis optica spectrum disorder. Drugs. 2020;80(7):719-727. doi:10.1007/s40265-020-01297-w

2. Soliris. Package insert. Alexion Pharmaceuticals Inc.; 2020. Accessed October 14, 2021.

3. FDA approves first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system. News release. US Food and Drug Administration; June 27, 2019.

4. Neuromyelitis optica spectrum disorder. National Organization for Rare Disorders. Accessed October 14, 2021.

5. Hinson SR, Romero MF, Popescu BFG, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245-1250. doi:10.1073/pnas.1109980108

6. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614-625. doi:10.1056/NEJMoa1900866

Reviewed by Debjyoti Talukdar, MD, on 10/8/2021.

Reviewed by Debjyoti Talukdar, MD, on 10/7/2021.