UPLIZNA Mechanism of Action

UPLIZNA targets CD19-expressing B cells, a central driver of NMOSD activity1

UPLIZNA mechanism of action graphic UPLIZNA mechanism of action graphic UPLIZNA mechanism of action graphic

CD19 Targeting
NMOSD Immunopathogenesis
Molecular Design

CD19 Targeting

CD19+ cells are a primary cellular source of AQP4-IgG production2-4

Chart showing CD19 expression across B-cell lineage Chart showing CD19 expression across B-cell lineage

CD19 is expressed across the B-cell lineage2-4

Compare CD19 and CD20 expressions across the B-cell lineage

NMOSD Immunopathogenesis

UPLIZNA is thought to address the multifaceted immunopathogenesis of NMOSD, including1,5
UPLIZNA mechanism of action video preview
Autoantibody production icon

Autoantibody production1

Cytokine secretion icon

Cytokine secretion1

T-cell interactions icon

Antigen presentation1

Targeting icon

T-cell interactions1

Molecular Design

UPLIZNA is designed for efficacy and tolerability

Glycoengineered Design

  • Approximately 40% of the population is homozygous for a genetic risk factor that can diminish the efficacy of many monoclonal antibodies6,7
  • UPLIZNA was specifically glycoengineered to overcome this genetic barrier6
  • Glycoengineering involves removing the fucose sugar molecule, which allows for5,8,9:
    • Efficient binding of effector natural killer cells
    • Effective B-cell depletion without the need for dose adjustments

Efficacy of UPLIZNA was consistent regardless of genotype6

See the safety profile of UPLIZNA

Humanized Structure

UPLIZNA has humanized structure. Compared with chimeric structures, humanized structures are associated with5,10-12:

  • Reduced immunogenicity
  • Improved tolerability
  • Decreased potential infusion-related reactions

Efficacy of UPLIZNA was consistent regardless of genotype6

Selective Targeting

UPLIZNA is the only FDA-approved therapy for NMOSD that eliminates the primary cellular sources of AQP4-IgG production, including plasmablasts and some plasma cells.1-3,5 The precise mechanism by which UPLIZNA exerts its therapeutic effects in NMOSD is unknown.

Efficacy of UPLIZNA was consistent regardless of genotype6

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View the N-MOmentum study design

AQP4-IgG, aquaporin-4 immunoglobulin G; NMOSD, neuromyelitis optica spectrum disorder.

Tx Recommendations

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

UPLIZNA (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

  • A history of life-threatening infusion reaction to UPLIZNA
  • Active hepatitis B infection
  • Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

UPLIZNA (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

  • A history of life-threatening infusion reaction to UPLIZNA
  • Active hepatitis B infection
  • Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

  1. Bennett JL, O’Connor KC, Bar-Or A, et al. B lymphocytes in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e104. doi:10.1212/NXI.0000000000000104
  2. Forsthuber TG, Cimbora DM, Ratchford JN, Katz E, Stüve O. B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord. 2018;11:1-13. doi:10.1177/1756286418761697
  3. Baker D, Marta M, Pryce G, et al. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine. 2017;16:41-50. doi:10.1016/j.ebiom.2017.01.042
  4. Ho JWK, Koundinya R, Caetano TS, et al. Inferring differential leukocyte activity from antibody microarrays using a latent variable model. Genome Informatics. International Conference on Genome Informatics. 2008;21:126-137. doi:10.1142/9781848163324_0011
  5. UPLIZNA (inebilizumab-cdon) [prescribing information]. Horizon.
  6. Aktas O, Bennett JL, Winshenker BG, et al. Impact of low affinity IgG Fc region receptor III-A gene polymorphisms on neuromyelitis optica spectrum disorder treatment outcomes: N-MOmentum study. Poster NDM02 presented at: 16th World Congress on Controversies in Neurology (virtual); March 24-27, 2022.
  7. Kim S-H, Jeong IH, Hyun J-W, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 2015;72(9):989-995. doi:10.1001/jamaneurol.2015.1276
  8. Herbst R, Wang Y, Gallagher S, et al. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010;335(1):213-222. doi:10.1124/jpet.110.168062
  9. Ward E, Mittereder N, Kuta E, et al. A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo. Br J Haematol. 2011;155(4):426-437. doi:10.1111/j.1365-2141.2011.08857.x
  10. Cree BAC, Bennett JL, Kim HJ, et al. N-MOmentum study investigators. 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
  11. Hwang WYK, Foote J. Immunogenicity of engineered antibodies. Methods. 2005;36(1):3-10. doi:10.1016/j.ymeth.2005.01.001
  12. Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2(3):256-265. doi:10.4161/j.mabs.2.3.11641