INDICATIONS 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.

uplizna-logo

Choose Indication

Please select
Patient Enrollment Form
Request Support

You are now leaving UPLIZNAhcp.com

Horizon is not responsible for the content of external websites linked within UPLIZNAhcp.com.

Do you want to continue?

Yes No
info-icon

Days 1 through 21: prednisone 20 mg (or equivalent) taper1

minus-icon

Days 1 through 21: prednisone 20 mg (or equivalent) taper1

info-icon

Studied exclusively as monotherapy5

minus-icon

The majority of patients chose to enter the open-label period:
96% of patients who received UPLIZNA5
90% of patients randomized to placebo5

info-icon

The majority of patients chose to enter the open-label period:

96% of patients who received UPLIZNA5
90% of patients randomized to placebo5

minus-icon

Studied exclusively as monotherapy5

Layer_1

  • Full Study Description

    N-MOmentum was a phase 2/3, multicenter, double-blind, randomized (3:1) placebo-controlled trial with an OLP. The RCP studied 213 AQP4-IgG+ patients and 17 AQP4-IgG– patients for 6 months (197 days). Inclusion criteria specified adults diagnosed with NMOSD, an EDSS score ≤8.0, and a history of ≤1 attack requiring rescue therapy during the year before screening or ≥2 attacks requiring rescue therapy in the 2 years before screening.1,6

    • Well-defined primary endpoint: time to onset of attack beginning at Day 1 through Day 1971
    • Key secondary endpoints evaluated many aspects of living with NMOSD, including1:
    • Worsening of EDSS as defined by an increase of ≥2 from baseline of 0 to 1, increase of ≥1 from baseline of 1 to 5, or increase in ≥0.5 from baseline of ≥5.5
    • Cumulative MRI lesions, including new Gd-enhancing lesions and new or enlarging T2 lesions
    • Hospitalizations, defined as inpatient stays of ≥1 night
    • Changes in visual acuity as measured by low-contrast binocular score

    An Independent Data Monitoring Committee (IDMC) agreed that a placebo comparator and monotherapy design would best enable the evaluation of the efficacy and safety of UPLIZNA. Certain features reduced the risk to placebo-treated patients, including limiting the length of the RCP to 6.5 months and allowing placebo-treated subjects to immediately enter the OLP following an attack.5

Enrollment to the study was stopped at 231 patients when the IDMC determined that the efficacy of UPLIZNA was demonstrated, and no further patients should be given placebo treatment5

*In the AQP4-IgG+ patient population.5

†Due to a half-life of ≤24 hours, AZA and MMF were allowed up until Day 1. Rituximab was stopped 6 months prior to randomization, unless the patient had B-cell counts above the LLN.5

Inclusion Criteria

The inclusion criteria for N-MOmentum were designed to ensure the trial reflected the real-world patient population with NMOSD1

Inclusion_criteria_icon

Included 230 patients from 25
countries across 99 sites1

NMOSD_Walker_icon

Enrolled patients with an EDSS
score ≤8.0, the highest degree of disability permitted in NMOSD clinical trials6

Baseline characteristics in the AQP4-IgG+ population receiving UPLIZNA (n=161)5
  • Mean age: 43 years
  • Sex: 94% female
  • Race: 53% White, 23% Asian, 9% Black or African American, 7% American Indian or Alaskan Native, 8% Other
  • Ethnicity: 16% Hispanic or Latino
  • Mean EDSS (range=0 to 8.0): 3.81
  • Mean Gd-enhancing lesions: 1.2
  • Genetic mutations: 48% out of 142 patients who consented to genotyping had the F/F genotype for the receptor encoded by FCGR3A7

N-MOmentum featured the most robust attack adjudication process of any NMOSD trial1,5,8

The NMOSD-specific 18-point attack criteria ensured investigators captured any sign or symptom of a new attack, from the most subtle to the most severe1,5
  • Attack criteria accounted for all potential domains of disease activity1

Out of 22 investigator-determined attacks in AQP4-IgG+ patients on UPLIZNA in the RCP, only 4 (18.2%) were rejected by the adjudication committee8

Attack adjudication featured 18 comprehensive criteria across 4 distinct domains1
  • Optic Icon
    1 Landolt C Broken
    Ring Chart    		 >15-character drop in high-contrast LCBRC from last visit as measured in a previously affected eye and no other ophthalmological explanation
    2 Reduction of ≥2 steps in CF to NLP from last visit
    3 Reduction of ≥7 characters in
    low-contrast LCBRC from last visit    		 as measured in either eye alone (monocular) and a new RAPD in the affected eye
    4 Reduction of ≥7 characters in
    high-contrast LCBRC from last visit
    5 Reduction of ≥5 characters in
    low-contrast LCBRC from last visit    		 as measured in either eye alone (monocular) and loss of a previously documented RAPD in the fellow eye
    6 Reduction of ≥5 characters in
    high-contrast LCBRC from last visit
    7 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and a new RAPD in the affected eye
    8 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and loss of a previously documented RAPD in the fellow eye
    9 MRI Reduction of ≥7 characters in low-contrast LCBRC from last visit as measured in either eye alone (monocular) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
    10 Reduction of ≥5 characters in high-contrast LCBRC from last visit
    11 Reduction of ≥1 step in CF to NLP from last visit
    Landolt C Broken Ring Chart
    1 >15-character drop in high-contrast
    LCBRC from last visit    		 as measured in a previously affected eye and no other ophthalmological explanation
    2 Reduction of ≥2 steps in CF to NLP from last visit
    3 Reduction of ≥7 characters in
    low-contrast LCBRC from last visit    		 as measured in either eye alone (monocular) and a new RAPD in the affected eye
    4 Reduction of ≥7 characters in
    high-contrast LCBRC from last visit
    5 Reduction of ≥5 characters in
    low-contrast LCBRC from last visit    		 as measured in either eye alone (monocular) and loss of a previously documented RAPD in the fellow eye
    6 Reduction of ≥5 characters in
    high-contrast LCBRC from last visit
    7 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and a new RAPD in the affected eye
    8 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and loss of a previously documented RAPD in the fellow eye
    MRI
    9 Reduction of ≥7 characters in low-contrast LCBRC from last visit as measured in either eye alone (monocular) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
    10 Reduction of ≥5 characters in high-contrast LCBRC from last visit
    11 Reduction of ≥1 step in CF to NLP from last visit
  • Optic Icon
    12 FSS Worsening of ≥2 points as compared with last visit as measured in at least 1 of the relevant FSS (pyramidal, bladder/bowel, sensory)
    13 EDSS Worsening of ≥1 point as compared with last visit as measured by EDSS if previous score was ≥5.5
    14 MRI Worsening of ≥1 point as compared with last visit when the last visit score was ≥1 as measured in at least 2 of the relevant FSS (pyramidal, bladder/bowel, sensory) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord
    15 Worsening of ≥0.5 points score as compared with last visit if the previous score was ≥5.5 as measured by EDSS and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord
    FSS
    12 Worsening of ≥2 points as compared with last visit as measured in at least 1 of the relevant FSS (pyramidal, bladder/bowel, sensory)
    EDSS
    13 Worsening of ≥1 point as compared with last visit as measured by EDSS if previous score was ≥5.5
    MRI
    14 Worsening of ≥1 point as compared with last visit as measured in at least 2 of the relevant FSS (pyramidal, bladder/bowel, sensory) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord
    15 Worsening of ≥0.5 points score as compared with last visit if the previous score was ≥5.5 as measured by EDSS and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord
  • Optic Icon
    16 MRI Isolated (not present at last visit) intractable nausea, vomiting, and/or hiccups lasting >48 hours accompanied by a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain stem
    17 Worsening of ≥2 points as compared with last visit, with a score of ≥3 at the current visit as measured in at least one of the relevant FSS (cerebral, sensory, pyramidal) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with clinical presentation
    MRI
    16 Isolated (not present at last visit) intractable nausea, vomiting, and/or hiccups lasting >48 hours accompanied by a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain stem
    17 Worsening of ≥2 points as compared with last visit, with a score of ≥3 at the current visit as measured by EDSS and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord
  • Brain Icon
    18 MRI Worsening of ≥2 points as compared with last visit, with a score of ≥3 at the current visit as measured in at least one of the relevant FSS (cerebral, sensory, pyramidal) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation
    MRI
    18 Worsening of ≥2 points as compared with last visit, with a score of ≥3 at the current visit as measured in at least one of the relevant FSS (cerebral, sensory, pyramidal) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation

Optic neuritis, transverse myelitis, area postrema, acute brain stem syndrome, and symptomatic cerebral syndrome are part of the 6 core clinical characteristics of NMOSD9

See how UPLIZNA reduced NMOSD attacks6

AQP4-IgG, aquaporin-4 immunoglobulin G; AZA, azathioprine; CF, counting fingers; EDSS, Expanded Disability Status Scale; FCGR3A, Fc gamma receptor 3; FSS, functional systems score; Gd, gadolinium; ITT, intention-to-treat; LCBRC, Landolt C broken ring chart; LLN, lower limit of normal; MMF, mycophenolate mofetil; NLP, no light perception; NMOSD, neuromyelitis optica spectrum disorder; OLP, open-label period; RAPD, relative afferent pupillary defect; RCP, randomized controlled period.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS

UPLIZNA® (inebilizumab-cdon) is contraindicated in patients with a history of a life-threatening infusion reaction to UPLIZNA, active hepatitis B infection, or active or untreated latent tuberculosis. 

WARNINGS AND PRECAUTIONS

  • Infusion Reactions: Can cause infusion reactions, including anaphylaxis. Symptoms can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or palpitations. During the randomized clinical trial period (RCP), infusion reactions were observed with the first course of UPLIZNA in 9.3% of NMOSD patients. Infusion reactions of UPLIZNA were observed in 7.4% of IgG4-RD patients during the RCP. 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 antipyretic. For life-threatening infusion reactions, immediately and permanently stop UPLIZNA and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment. 
  • Infections: An increased risk of infections has been observed with other B-cell depleting therapies. The most common infections reported by UPLIZNA-treated patients in the NMOSD RCP and open-label clinical trial periods were urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). In the IgG4-RD RCP and open-label period, the most common infections reported by UPLIZNA-treated patients were upper respiratory tract infection (11%), nasopharyngitis (10%), urinary tract infection (9%), and influenza (6%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved. 

    Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants: UPLIZNA has not been studied in combination with other immunosuppressants. If combining UPLIZNA with another immunosuppressive therapy, consider the potential for increased immunosuppressive effects. 

    Hepatitis B Virus (HBV) Reactivation: Risk of HBV reactivation has been observed with other B-cell depleting antibodies. There have been no cases of HBV reactivation in patients treated with UPLIZNA, but patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment. Do not administer to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

    Progressive Multifocal Leukoencephalopathy (PML): Although no confirmed cases of 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. In UPLIZNA clinical trials one subject died following the development of new brain lesions for which a definitive diagnosis could not be established, though the differential diagnosis included an atypical NMOSD relapse, PML, or acute disseminated encephalomyelitis. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. 

    Tuberculosis
    Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA. Consider anti-tuberculosis therapy prior to initiation of UPLIZNA in patients with a history of latent active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment.

    Vaccinations
    Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of UPLIZNA. The safety of immunization with live or live-attenuated vaccines following UPLIZNA therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. 
    Vaccination of Infants Born to Mothers Treated with UPLIZNA During Pregnancy
    In infants of mothers exposed to UPLIZNA during pregnancy, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in these exposed infants may increase the risks from live or live-attenuated vaccines.  Non-live vaccines, as indicated, may be administered prior to recovery from B-cell and immunoglobulin level depletion, but consultation with a qualified specialist should be considered to assess whether a protective immune response was mounted.
  • Reductions 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 levels of quantitative serum immunoglobulins during treatment with UPLIZNA, especially in patients with opportunistic or recurrent infections, and until B-cell repletion after discontinuation of therapy. Consider discontinuing UPLIZNA therapy if a patient with low immunoglobulin G or M develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins. 
  • Fetal Risk: Based on animal data, UPLIZNA can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to UPLIZNA even after B-cell repletion. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception while receiving UPLIZNA and for at least 6 months after the last dose. 

ADVERSE REACTIONS

  • The most common adverse reactions in NMOSD (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.
  • The most common adverse reactions in IgG4-RD (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infections and lymphopenia. 

INDICATIONS

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.

UPLIZNA® is indicated for the treatment of Immunoglobulin G4-related disease (IgG4-RD) in adult patients.

Please see UPLIZNA Full Prescribing Information.

IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS

UPLIZNA® (inebilizumab-cdon) is contraindicated in patients with a history of a life-threatening infusion reaction to UPLIZNA, active hepatitis B infection, or active or untreated latent tuberculosis. 

WARNINGS AND PRECAUTIONS 

  • Infusion Reactions: Can cause infusion reactions, including anaphylaxis. Symptoms can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or palpitations. During the randomized clinical trial period (RCP), infusion reactions were observed with the first course of UPLIZNA in 9.3% of NMOSD patients. Infusion reactions of UPLIZNA were observed in 7.4% of IgG4-RD patients during the RCP. 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 antipyretic. For life-threatening infusion reactions, immediately and permanently stop UPLIZNA and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

  • Infections: An increased risk of infections has been observed with other B-cell depleting therapies. The most common infections reported by UPLIZNA-treated patients in the NMOSD RCP and open-label clinical trial periods were urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). In the IgG4-RD RCP and open-label period, the most common infections reported by UPLIZNA-treated patients were upper respiratory tract infection (11%), nasopharyngitis (10%), urinary tract infection (9%), and influenza (6%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

    Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants: UPLIZNA has not been studied in combination with other immunosuppressants. If combining UPLIZNA with another immunosuppressive therapy, consider the potential for increased immunosuppressive effects. 

    Hepatitis B Virus (HBV) Reactivation: Risk of HBV reactivation has been observed with other B-cell depleting antibodies. There have been no cases of HBV reactivation in patients treated with UPLIZNA, but patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment. Do not administer to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment. 

    Progressive Multifocal Leukoencephalopathy (PML): Although no confirmed cases of 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. In UPLIZNA clinical trials one subject died following the development of new brain lesions for which a definitive diagnosis could not be established, though the differential diagnosis included an atypical NMOSD relapse, PML, or acute disseminated encephalomyelitis. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. 

    Tuberculosis
    Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA. Consider anti-tuberculosis therapy prior to initiation of UPLIZNA in patients with a history of latent active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. 

    Vaccinations
    Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of UPLIZNA. The safety of immunization with live or live-attenuated vaccines following UPLIZNA therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. 
    Vaccination of Infants Born to Mothers Treated with UPLIZNA During Pregnancy
    In infants of mothers exposed to UPLIZNA during pregnancy, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in these exposed infants may increase the risks from live or live-attenuated vaccines.  Non-live vaccines, as indicated, may be administered prior to recovery from B-cell and immunoglobulin level depletion, but consultation with a qualified specialist should be considered to assess whether a protective immune response was mounted.
  • Reductions 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 levels of quantitative serum immunoglobulins during treatment with UPLIZNA, especially in patients with opportunistic or recurrent infections, and until B-cell repletion after discontinuation of therapy. Consider discontinuing UPLIZNA therapy if a patient with low immunoglobulin G or M develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.
  • Fetal Risk: BBased on animal data, UPLIZNA can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to UPLIZNA even after B-cell repletion. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception while receiving UPLIZNA and for at least 6 months after the last dose..

ADVERSE REACTIONS

  • The most common adverse reactions in NMOSD (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia. 
  • The most common adverse reactions in IgG4-RD (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infections and lymphopenia.

INDICATIONS

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.

UPLIZNA® is indicated for the treatment of Immunoglobulin G4-related disease (IgG4-RD) in adult patients.

Please see UPLIZNA Full Prescribing Information.

  • REFERENCES:
    1. Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomized placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352-1363. doi:10.1016/S0140-6736(19)31817-3
    2. ENSPRYNG® (satralizumab-mwge) [prescribing information] Genentech, Inc.
    3. SOLIRIS® (eculizumab) [prescribing information] Alexion Pharmaceuticals, Inc.
    4. ULTOMIRIS® (ravulizumab-cwvz) [prescribing information]. Alexion Pharmaceuticals, Inc.
    5. Data on File. Horizon; June 2021.
    6. UPLIZNA (inebilizumab-cdon) [prescribing information] Horizon.
    7. Kim HJ, Aktas O, Patterson KR, et al. Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism. Ann Clin Transl Neurol. 2023;10(12):2413-2420. doi:10.1002/acn3.51911
    8. Cree BAC, Greenberg B, Cameron C, Weinshenker BG. Letter to the Editor Regarding “Network meta-analysis of Food and Drug Administration-approved treatment options for adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder.” Neurol Ther. 2022;11(3):1439-1443. doi:10.1007/s40120-022-00376-2
    9. Wingerchuk DM, Banwell B, Bennett JL, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:0.1212/WNL.0000000000001729