Inebilizumab Has Enduring Effect as NMOSD Treatment

Author(s):

Patients in the randomized controlled trial and the open-label extension treated with inebilizumab experienced similar rates of being attack-free, extending as far as 4 years.

Bruce Cree, MD, PhD, MCR, FAAN

Two-year data from the open-label extension (OLE) of the N-MOmentum trial (NCT02200770) showed that inebilizumab (Uplizna; Viela Bio), an FDA-approved treatment for neuromyelitis optica spectrum disorder (NMOSD), continued to provide benefits similar to those seen in the randomized controlled period (RCP).¹

The results were presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, by Bruce Cree, MD, PhD, MCR, FAAN, clinical research director, UCSF Multiple Sclerosis Center, and professor of clinical neurology, UCSF Weill Institute for Neurosciences.

In total, 216 of the 230 participants initially randomized and dosed opted to enter the OLE where they received inebilizumab 300 mg every 28 weeks for at least 2 years. In both the RCP and the OLE, 87.7% of patients receiving inebilizumab remained attack-free; however, those in the OLE remained attack-free for up to 4 years.

In comparison, 60.7% and 83.4% of those on placebo remained attack-free in the RCP and OLE, respectively. At OLE baseline, mean Expanded Disability Status Scale (EDSS) scores were lower in the group randomized to inebilizumab compared to those in the placebo group (3.82 [standard deviation (SD), 1.76] versus 4.16 [SD, 1.71]). By OLE week 78, patients randomized to either group demonstrated lower EDSS scores than recorded at baseline (inebilizumab: –0.24 [SD, 0.87]; placebo: –0.12 [SD, 0.73]).

A separate analysis evaluated the long-term safety outcomes with inebilizumab during the OLE of the N-MOmentum trial. Among the placebo and inebilizumab groups, mean exposure was 2.4 (SD, 1.1) and 2.3 (SD, 1.1) years.²

Treatment-emergent adverse event (TEAE) incidence rates per 100 person-years were 304.5 and 251.4 in the placebo and inebilizumab groups, respectively. Urinary tract infection (UTI) was the most common (placebo: 14.9%; inebilizumab: 7.2%), followed by nasopharyngitis (placebo: 7.1%; inebilizumab: 6.9%) and upper respiratory tract infection (placebo: 4.7%; inebilizumab: 5.7%).

The most common treatment-emergent serious adverse events (TESAEs) were UTI (placebo: 4.7%; inebilizumab: 0.5%) and pneumonia (placebo: 0.8%; inebilizumab: 0.7%). Infused-related reactions (IRRs) occurred in 6 (11.8%) patients randomized to placebo and 9 (5.5%) patients treated with inebilizumab.

Notably, 2 patients in the OLE died. The first was from complications of a severe NMOSD attack and the other from a central nervous system (CNS) event of unclear etiology. No other deaths occurred.

Inebilizumab is a humanized monoclonal antibody designed to bind with high affinity to CD19 and deplete a broad range of B cells, including autoantibody-secreting plasma blasts and CD19-expressing plasma cells. In the original RCP, risk of NMOSD relapse was reduced by 77% in the treatment group compared with placebo.³

The trial consisted of 231 patients with NMOSD, including those with and without anti-aquaporin-4 (AQP4) antibodies, which occur in about 80% of patients with NMOSD. In addition to the benefits shown by inebilizumab, researchers also found that serum glial fibrillary acidic protein (sGFAP) is an accurate biomarker of NMOSD activity, attack risk, and treatment effects.

Participants with sGFAP concentrations of at least 170 mg/mL (≥2 SDs above health donor mean concentration) had a 3-fold greater chance of adjudicated attack than participants with lower baseline concentrations (hazard ratio [HR], 3.09 [95% CI, 1.57-6.10] P = .001).

The FDA approved inebilizumab for the treatment of NMOSD in adults who are AQP4 antibody positive in June 2020, marking the second treatment approved for patients with NMOSD.⁴ It originally received breakthrough therapy designation from the FDA in April 2019 based on findings from the N-MOmentum study, the largest ever monotherapy study in this patient population.

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REFERENCES

1. Cree B, Bennett J, Weinshenker B, et al. Long-term efficacy outcomes with inebilizumab treatment in NMOSD: the N-MOmentum trial. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P15.076

2. Cree B, Bennett J, Weinshenker B, et al. Long-term safety outcomes with inebilizumab treatment in NMOSD: the N-MOmentum trial. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P15.100

3. Aktas O, Smith MA, Rees WA, et al. Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol. Published online March 16, 2021. doi: 10.1002/ana.26067

4. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. News release. FDA. June 11, 2020. Accessed April 20, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-rare-disease-affecting-optic-nerve-spinal-cord