Neuromyelitis Optica Spectrum Disorder (NMOSD)

Soliris (Eculizumab)

Soliris® (eculizumab) is a late complement inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Soliris is also FDA-approved for the treatment of adults with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis, paroxysmal nocturnal hemoglobinuria (NPH), and atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.1 Soliris binds to complement component C5 and inhibits formation of the C5b-induced membrane attack complex.2 

The efficacy of Soliris was established in a randomized, double-blind, placebo-controlled trial of 143 patients with anti-AQP4-positive NMOSD. Relative risk reduction in the adjudicated on-trial annualized relapse rate was 96% in the treatment arm in comparison with the placebo arm. Improvement in patients in the treatment arm was documented in those with and without concomitant immunosuppressive therapy. Additionally, patients in the treatment arm had a reduced annualized rate of hospitalization (0.04 vs 0.31 for placebo), corticosteroid administration to treat acute relapses (0.07 vs 0.42 for placebo), and plasma exchange or fresh frozen plasma infusion (0.02 vs 0.19 for placebo).1

Recent articles about Soliris

Soliris limits the ability of the immune system to combat infections caused by Neisseria and other species of encapsulated bacteria. It should not be used in patients with serious, unresolved Neisseria meningitidis infection or those who are not currently vaccinated against N meningitidis. Immunization with meningococcal vaccines at least 2 weeks before administration of the first dose is recommended. Patients with complement deficiencies should be vaccinated for meningococcal disease according to the most current Advisory Committee on Immunization Practices (ACIP) guidelines. In unvaccinated patients, Soliris should be withheld unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection (septicemia and/or meningitis).1

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Ultomiris (Ravulizumab-cwvz)

Ultomiris™, a modified form of eculizumab, is a long-acting complement inhibitor with a reduced affinity for C5 at endosomal pH. This drug has been developed to address the dosing limitation associated with eculizumab, which must be administered intravenously at weekly intervals initially, then intravenously every 2 weeks. The modifications allow Ultomiris to bind C5 at physiologic pH but dissociate from it once inside the acidic environment of an endosome. The antibody detaches from C5 inside the endosome, evades lysosomal degradation, and is recycled. The increased half-life of ravulizumab allows less-frequent dosing, at once every 8 weeks. Currently, Ultomiris is not FDA-approved for the treatment of NMOSD. An external placebo-controlled, open-label phase 3 trial is underway to determine the efficacy of Ultomiris in patients wth AQP4-positive NMOSD (NCT04201262). The expected completion date is July 2024.3

Other Potential Agents 

Given the success of eculizumab for the treatment of NMOSD, other complement inhibitors, such as ravulizumab, are being studied as potential treatment options. Novel complement-blocking agents currently under investigation for the treatment of diseases characterized by complement-mediated damage, such as NPH and cold agglutinin disease, may be used to treat NMOSD in the future. Examples of such agents are discussed below.

Crovalimab is another modified form of eculizumab with the same mechanism of action as Ultomiris. It is being evaluated in a phase 3 trial as a potential therapeutic option for patients with NPH (NCT04432584).4  

Nomacopan is also a C5 inhibitor. Like eculizumab, it prevents C5 cleavage but binds C5 at a different site. Nomacopan is currently being investigated in a phase 2 study as a treatment for NPH. The advantage of nomacopan is that it can be self-administered via the subcutaneous route.4 

Sutimlimab is a humanized monoclonal antibody targeting C1s. It is currently under investigation in a phase 3 trial as a treatment for cold agglutinin disease.4  

APL-2 and AMY-101 may be agents for complement modulator therapy. They target 3C, inhibiting its conversion to C3 convertase, and have shown acceptable safety profiles in early staged clinical trials.4 

Vilobelimab (IFX-1) is a neutralizing monoclonal antibody that targets C5a. It is currently under investigation as a treatment option for hidradenitis suppurativa, pyoderma gangrenosum, and severe COVID-19.4 


1. SOLIRIS® (eculizumab). Prescribing information. New Haven, CT: Alexion Pharmaceuticals; 2017.

2. Dubois EA, Cohen AF. Eculizumab. Br J Clin Pharmacol. 2009;68(3):318. doi:10.1111/j.1365-2125.2009.03491.x

3. A Phase 3, External Placebo-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD). NCT04201262. Accessed March 2, 2022.

4. Asavapanumas N, Tradtranstip L, Verkman AS. Targeting the complement system in neuromyelitis optica spectrum disorder. Expert Opin Biol Ther. 2021;21(8):1073-1086. doi:10.1080/14712598.2021.1884223

Reviewed by Debjyoti Talukdar, MD, on 3/5/2022.