Neuromyelitis Optica Spectrum Disorder (NMOSD)

Uplizna® (inebilizumab-cdon) is a cytolytic monoclonal antibody directed against CD19. It is indicated for the treatment of adult patients with antiaquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD).1 NMOSD is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis and transverse myelitis. These attacks often lead to permanent blindness and impaired mobility.2,3 The active pharmaceutical ingredient of Uplizna is inebilizumab (inebilizumab-cdon in the United States), developed by Viela Bio, which was later acquired by Horizon Therapeutics.1,3 Uplizna was first approved for the treatment of NMOSD in the United States in June 2020.3

Mechanism of Action and Use of Inebilizumab

The exact mechanism of action of inebilizumab remains elusive; however, it may involve drug binding to pre-B and mature B lymphocytes.3 CD19+ B cells have been shown to be important in the immunopathogenesis of NMOSD, producing AQP4 autoantibodies that target the AQP4 protein expressed on astrocytes of the CNS. Drug binding to this protein leads to cell injury through a complement-mediated pathway.4 Inebilizumab is a humanized, affinity-optimized, afucosylated CD19+ immunoglobulin G1 (IgG1) that binds to the surface of CD19+ B cells and activates the Fcγ receptor, mediating antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis.4,5

Inebilizumab is supplied in single-dose vials at a concentration of 100 mg/10 mL and is administered as an intravenous infusion. The recommended initial dose is 300 mg administered 2 times 2 weeks apart. Beginning at 6 months following the first dose, a single 300-mg intravenous solution of inebilizumab should be administered every 6 months.1 Patients should be monitored during and for 1 hour after the infusion.6 Before the first administration, patients must be screened for infections such as hepatitis B and tuberculosis because the drug is contraindicated for persons with active hepatitis B virus infection or with active or untreated tuberculosis.1,3 The continued use of inebilizumab may induce a progressive and prolonged decline of IgG and IgM titers.1

Access the Uplinza monograph page at MPR for full prescribing information.

The administration of inebilizumab can cause infusion reactions manifesting as headache, nausea, fever, muscle pain, sleepiness, and rash. These reactions are most common after the first infusion and are mild to moderate.1,7 Steroids, antihistamines, and antipyretic medications can be prescribed by the medical team and administered before an infusion to reduce the frequency and severity of potential reactions. Administering inebilizumab simultaneously with immunosuppressants such as corticosteroids can increase the risk for infections.1 The drug is degraded by proteolytic enzymes distributed throughout the body.1

Inebilizumab in Clinical Trials

The safety and efficacy of Inebilizumab were evaluated in the N-MOmentum study (NCT02200770), a multinational placebo-controlled, randomized (3:1), double-blind clinical trial.8 This phase II/III study enrolled 213 anti-AQP4 antibody-positive patients and 17 anti-AQP4 antibody-negative patients. The trial included patients with newly diagnosed disease and patients who presented with severe disease. Inebilizumab was administered to 161 of the anti-AQP4 antibody-positive patients as 2 single 300-mg intravenous infusions 2 weeks apart, while 52 of the anti-AQP4 antibody-positive patients received a placebo. The primary efficacy endpoint was time to the first adjudicated relapse on or before day 197. The time to onset of an NMOSD attack was significantly longer in the patients treated with inebilizumab than in those who received placebo (relative risk reduction, 77%).1 In addition, in comparison with the patients who received placebo, the treated patients had reduced annualized rates of hospitalization (.11 for Uplizna vs .50 for placebo).1 The trial also showed a rapid depletion of the CD20+ B-cell count, a surrogate marker for the CD19+ cell count, which was significantly decreased at 1 week following administration and remained below the lower limit of normal for 4 weeks.1,8 This cell count remained below the lower limit of normal in 94% of the patients for 28 weeks after the start of treatment. The number of relapses was also reduced in 89% of the patients after 28 weeks of Inebilizumab treatment.1 

During the N-MOmentum trial, the intravenous administration of inebilizumab was generally well tolerated. Adverse events observed in at least 5% of the participants included urinary tract infection, arthralgia, headache, and back pain. Urinary tract infection and arthralgia were the most common adverse reactions during this trial.1


1. Uplizna (inebilizumab-cdon) prescribing information. Horizon Therapeutics; July 2021. Accessed October 20, 2021.

2. Neuromyelitis optica spectrum disorder. National Organization for Rare Disorders (NORD). Accessed October 20, 2021.

3. Frampton JE. Inebilizumab: first approval. Drugs. 2020;80(12):1259-1264. doi:10.1007/s40265-020-01370-4

4. Ali F, Sharma K, Anjum V, Ali A. Inebilizumab-cdon: USFDA approval for the treatment of NMOSD (neuromyelitis optica spectrum disorder). Curr Drug Discov Technol. Published online May 18, 2021. doi:10.2174/1570163818666210519103001

5. Proposed mechanism of action. Horizon Therapeutics, 2021. Accessed October 20, 2021.

6. Dosing. Horizon Therapeutics; 2021. Accessed October 20, 2021.

7. Efficacy and safety. Horizon Therapeutics; 2021. Accessed October 20, 2021.

8. 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

Reviewed by Kyle Habet, MD