Health Canada Approves Inebilizumab as Treatment for Neuromyelitis Optica Spectrum Disorder

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In recent news, Health Canada approved inebilizumab for adult patients with neuromyelitis optica spectrum disorder who are anti-aquaporin-4 antibody positive, using results from the N-MOmentum trial as the basis for the approval.

Sumaira Ahmed, an NMOSD patient, founder and executive director of The Sumaira Foundation

Sumaira Ahmed

According to a recent announcement, Health Canada has granted approval of inebilizumab (Uplizna; Horizon Therapeutics) as an injection monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.1 The humanized, monoclonal antibody is designed to bind with high affinity to CD19 and deplete a broad range of B cells, including autoantibody-secreting plasmablasts and CD19-expressing plasma cells.

The agency based its approval on findings from the phase 2/3 N-MOmentum pivotal trial (NCT02200770) that assessed the safety and tolerability of inebilizumab in patients with NMOSD. In the trial, 21 of 174 (12%) participants who received inebilizumab had an attack compared with 22 of 56 (39%) patients who received placebo (HR, 0.272; 95% CI, 0.150–0.496; P <.0001). Notably, 87.6% of patients in the AQP4-IgG+ group remained relapse-free during the 5-month period post-treatment.2

“I think this is a huge milestone for patients, caregivers, and clinicians in the Canadian community. I think this approval symbolizes hope for the future because now there will be options for patients to choose what therapy works best for them, giving them the opportunity to live a higher quality of life," Sumaira Ahmed, an NMOSD patient, founder and executive director of The Sumaira Foundation, told NeurologyLive®. "I think it's a huge beacon of hope and I'm very excited for the Canadian community to have options for therapies that are designed for their diseases."

The N-MOmentum study was a multicenter, double-blind, randomized, placebo-controlled trial with an open-label extension period (OLP).2 Eligible participants were randomized (3:1) to receive 300 mg intravenous (IV) inebilizumab or placebo on days 1 and 15. All patients who completed the double-blind period continued on to the OLP where (n = 230) they received inebilizumab 300 mg IV for at least 2 years.

"I think that the approval of this particular therapy will inevitably make it easier for other therapies in the pipeline to get approval, and also encourage patients to participate in clinical trials in Canada because it exemplifies that when all stakeholders come together as a community, we can finally have a treatment for us. So, I'm excited," Ahmed told.

Presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, 2-year data from the OLE of the N-MOmentum showed that inebilizumab continued to provide benefits similar to those seen in the RCP.3 In comparison, 60.7% those on placebo remained attack-free in the RCP vs 83.4% of those who crossed over to active treatment in the OLE . At OLE baseline, mean Expanded Disability Status Scale (EDSS) scores were lower in the group randomized to inebilizumab compared with those originally 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. 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 TEAE (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 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.

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

"Options for patients with rare diseases are something you don't hear about often because there are not a lot that have a treatment indicated for the disease. The fact that NMOSD now has 3, almost 4 FDA approved therapies in the US at least is a unique experience for the rare disease community," Ahmed told. "We're very lucky but as I always say, 'what good is it to have therapies that are available and designed for us if they're not accessible to us.' Having those therapies is a good first step but now making it available to the patient so that they can benefit from those therapies is a very critical step in ensuring a positive and healthy pathway for the rare disease community."

REFERENCES
1. Health Canada Approves UPLIZNA® (inebilizumab for injection) for the Treatment of Neuromyelitis Optica Spectrum Disorders (NMOSD). News Release. Horizon Therapeutics. Published January 16, 2024. Accessed January 25, 2024. https://www.newswire.ca/news-releases/health-canada-approves-uplizna-r-inebilizumab-for-injection-for-the-treatment-of-neuromyelitis-optica-spectrum-disorders-nmosd--885268847.html
2. 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
3. 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
4. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. News release. FDA. June 11, 2020. Accessed January 25, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-rare-disease-affecting-optic-nerve-spinal-cord
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