Eculizumab Is Approved for Treatment of Neuromyelitis Optica Spectrum Disorder


The FDA approval was based on data from the phase 3 PREVENT trial in which 98% of patients treated with eculizumab were relapse free.

Sean J. Pittock, MD

Sean J. Pittock, MD

The US FDA has approved eculizumab (Soliris, Alexion) for the treatment of anti-aquaporin-4 antibody positive (AQP4-IgG-positive) neuromyelitis optica spectrum disorder (NMOSD), which accounts for nearly three-quarters of the population with NMOSD.1

The approval, which is the first of its kind, followed a 6-month priority review based on data from the PREVENT trial, which demonstrated safety and efficacy of eculizumab in adults and met its primary endpoint of prolonging time to first relapse and reducing risk of relapse.

Those data, which were presented at the recent Annual Meeting of the American Academy of Neurology in May and simultaneously published in the New England Journal of Medicine,2 solidified eculizumab as a novel treatment option for patients with the disease.

“NMOSD is a serious disease with devastating consequences,” said Michael Levy, MD, PhD, a consultant for Alexion and associate professor of neurology at Massachusetts General Hospital in Boston. “Each attack can result in potentially irreversible consequences—causing blindness or losing the ability to walk—so preventing relapse is the primary goal of treatment. With the approval of SOLIRIS, there is now for the first time an FDA-approved treatment available to NMOSD patients to help reduce the risk of relapse.”

The autoimmune disease attacks the central nervous system and accumulates damage to the brain, spinal cord, and optic nerve; it disproportionately affects young women, with an average age of 39. Notably, African American women face an increased risk for diagnosis with NMOSD as well as more frequent relapses. An additional challenge is that NMOSD is often misdiagnosed as multiple sclerosis due to observed broad demyelination and neuronal death; this can delay diagnosis and contribute to addition disability.

The PREVENT trial, led by Sean J. Pittock, MD, of Mayo Clinic, was a randomized, double-blind, placebo-controlled trial of 143 adults with AQP4-IgG-positive NMOSD. The participants (91% women) were randomly assigned to receive either intravenous eculizumab (900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks) or matched placebo. Baseline annualized relapse rate for the previous 24 months was 1.99±0.94, and median scores on the Expanded Disability Status Scale (EDSS), modified Rankin scale, and Hauser Ambulation Index showed moderate to severe disability.

The primary end point of adjudicated relapse occurred in 3 of 96 patients (3%) in the eculizumab group compared with 20 of 47 patients (43%) in the placebo group (hazard ratio 0.06; 95% CI, 0.02-0.20; P <.001). The median time to first relapse was not reached in the treatment group, but occurred at 103 weeks in the placebo group; most relapses were of myelitis.

In a subgroup analysis of patients not receiving immunosuppressive therapy, no patients in the eculizumab group experienced adjudicated relapse (0/21) compared with 54% of patients (7/13) in the placebo group.

The most common adverse events observed in the PREVENT trial were upper respiratory tract infection, nasopharyngitis, diarrhea, back pain, and dizziness. Serious adverse events included pneumonia, cellulitis, sepsis, and urinary tract infection. Notably, no cases of meningococcal infection were reported.

“For decades, we have been hoping for a therapy that can prevent relapse and subsequent accumulation of disability by addressing a critical underlying cause of the disease,” said Michael Levy, MD, PhD, associate professor and director of the Neuromyelitis Optica Clinic at Johns Hopkins University, in a statement at the time of publication.3 “The substantial effect of Soliris® seen in this groundbreaking randomized, controlled study in NMOSD could potentially become a turning point for patients and their families who live in constant fear of relapse.”

Of note, Soliris has a boxed warning for the risk of development of life-threatening and fatal meningococcal infections. The FDA advised that patients should be monitored for early signs of infection and be evaluated immediately upon showing any signs of infection. Treatment with Soliris should be discontinued in these patients, and use of Soliris in patients with a history of any other infection should be evaluated cautiously.

The drug will be made available through a Risk Evaluation and Mitigation Strategy (REMS) program in which prescribers must enroll. Prescribers are required to counsel patients on the risks of taking the drug and provide them with REMS education materials, as well as ensure that patients are vaccinated with the meningoccocal vaccine.


1. Alexion receives FDA approval of Soliris® (eculizumab) for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive [news release]. Boston: Alexion Pharmaceuticals. Published June 27, 2019. Accessed June 27, 2019.

2. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. Published online May 3, 2019. doi: 10.1056/NEJMoa1900866

3. Alexion Announces Successful Phase 3 PREVENT Study Of Soliris® (Eculizumab) In Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD) [news release]. Boston, MA: Alexion Pharmaceuticals. September 24, 2018. Accessed May 1, 2019.

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