Inebilizumab is superior to placebo in reducing the risk for an neuromyelitis optica spectrum disorder (NMOSD) attack, disability worsening, lesion activity on imaging, and disease-related hospitalizations in patients with NMOSD, according to study results published in The Lancet.

Currently, there are no approved therapies for NMOSD, a severe autoimmune, inflammatory central nervous system (CNS) disease that presents with optic neuritis and transverse myelitis. NMOSD attacks may be fatal as a result of secondary respiratory failure. The goal of this study was to investigate the safety and efficacy of inebilizumab, an anti-CD19, B cell-depleting antibody, as a monotherapy in reducing the risk for attacks and disability in NMOSD.

The multicenter double-blind randomized placebo-controlled phase 2/3 trial included patients from 99 outpatient specialty clinics or hospitals in 25 countries between January 6, 2015 and September 24, 2018. All participants were aged >18 years with a diagnosis of NMOSD and a history of at least 1 attack requiring rescue therapy in the year before screening or 2 attacks in the 2 years before screening.

The participants were randomly assigned to receive either inebilizumab (300 mg intravenously administered on days 1 and 15) or placebo. The primary outcome was time to onset of an NMOSD attack.

The study cohort included 230 patients (91% women, 52% white, 93% seropositive for anti-aquaporin-4 antibodies); 174 received inebilizumab and 56 received placebo.

Enrollment was planned to stop when 67 adjudicated attacks had occurred, 252 participants had been randomly allocated and dosed, or following a data monitoring committee recommendation, whichever occurred first. An interim futility analysis was preplanned for when half the number of expected attacks had occurred. 

The study met the primary end point, with a significant increase in time to onset of an NMOSD attack with inebilizumab compared with placebo. Because of a clear demonstration of efficacy, the randomized controlled period was stopped before complete enrollment, as recommended by the independent data-monitoring committee.

Attack was documented in 21 of 174 participants (12%) receiving inebilizumab compared with 22 (39%) of 56 participants receiving placebo (hazard ratio [HR], 0.272 [95% CI, 0.150-0.496]; P <.001). The number needed to treat was 3.73 (95% CI, 3.06–5.66).

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Adverse events occurred in 125 of 174 participants (72%) receiving inebilizumab and 41 of 56 participants (73%) receiving placebo. Serious adverse events occurred in 8 of 174 participants (5%) receiving inebilizumab and 5 of 56 participants (9%) receiving placebo; no serious adverse events were reported in more than 1 participant.

The study had several limitations, according to the researchers, including a relatively small sample size, exclusion of patients with a number of comorbidities, and a limited follow-up period.

“Although longer-term efficacy and safety data are needed, the positive results seen with inebilizumab and the emergence of other developmental therapies have the potential to provide a useful range of treatment options and to establish a new therapeutic landscape for NMOSD,” concluded the researchers.

Disclosure: This clinical trial was supported by MedImmune and Viela Bio. Please see the original reference for a full list of authors’ disclosures.

Reference

Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352-1363. doi:10.1016/S0140-6736(19)31817-3