Study Design

N-MOmentum: Proof Through Rigor

The largest, most diverse trial in NMOSD to date, N-MOmentum, offers unprecedented size (N=230) and length (4+ years)1,6a

Graphic illustrating the UPLIZNA N‐MOmentum study design

Graphic illustrating the UPLIZNA N‐MOmentum study design

  • N-MOmentum assessed long-term treatment with UPLIZNA, with nearly all patients who were randomized to UPLIZNA (96%, n=201) choosing to participate in a 4+ year open-label period6
  • UPLIZNA was studied exclusively as a monotherapy, with all patients stopping other immunosuppressants at randomization7
  • Well-defined primary endpoint: time to onset of attack beginning at day 1 through day 197
  • Secondary endpoints included comprehensive measurements evaluating many aspects of living with NMOSD, including EDSS, MRI lesions, hospitalizations, and visual acuity1

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

Study design icon
  • Included 230 patients from 25 countries across 99 sites1
  • Enrolled patients with an EDSS score ≤8.0, the highest degree of disability studied in NMOSD clinical trials7
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The well-defined 18-point attack criteria used in N-MOmentum maximized the ability of study investigators to capture possible signs of a new attack among the patient population1,6

  • The attack criteria accounted for all potential domains of disease activity (optic neuritis, myelitis, brain, and brain stem) and varying levels of severity, from modest symptoms requiring MRI confirmation to severe clinical attacks1

  • When assessing potential attacks, N-MOmentum had the highest level of agreement between trial investigators and attack adjudication committee in any NMOSD trial to date9

    • Out of 22 investigator-determined attacks in patients on UPLIZNA in the RCP, only 4 (13.6%) were rejected by the adjudication committee9

OPTIC NEURITIS Symptoms: blurred vision, loss of vision, eye pain
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 as measured in either eye alone (monocular) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
11 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
MYELITIS Symptoms: deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign (not in isolation)
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
BRAIN STEM Symptoms: nausea, intractable vomiting, intractable hiccups, other neurological signs (eg, double vision, dysarthria, dysphagia, vertigo, oculomotor nerve palsy, weakness, nystagmus, other cranial nerve abnormality)
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
BRAIN Symptoms: encephalopathy, hypothalmic dysfunction
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
OPTIC NEURITIS Symptoms: blurred vision, loss of vision, eye pain
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 as measured in either eye alone (monocular) and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
11 Reduction of ≥1 step in CF to NLP from last visit as measured in a previously affected eye and a new Gd-enhancing or new/enlarging T2 MRI lesion in the corresponding optic nerve
MYELITIS Symptoms: deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign (not in isolation)
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 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
BRAIN STEM Symptoms: nausea, intractable vomiting, intractable hiccups, other neurological signs (eg, double vision, dysarthria, dysphagia, vertigo, oculomotor nerve palsy, weakness, nystagmus, other cranial nerve abnormality)
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 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
BRAIN Symptoms: encephalopathy, hypothalmic dysfunction
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 new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation

aN-MOmentum was a phase 2/3, multicenter, double-blind, randomized (3:1) placebo-controlled trial with an open-label period. The randomized controlled period studied 213 AQP4-IgG+ patients and 17 AQP4-IgG- patients for 6 months (197 days). Inclusion criteria specified adults diagnosed with NMOSD, 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.1,7

CF, counting fingers; EDSS, expanded disability status scale; FSS, functional systems score; Gd, gadolinium; LCBRC, Landolt C broken ring chart; NLP, no light perception; NMOSD, neuromyelitis optica spectrum disorder; RAPD, relative afferent pupillary defect; RCP, randomized controlled period.

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. 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
  2. Rensel M, Zabeti A, Mealy MA, et al. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ≥4 years in the N-MOmentum trial. Mult Scler. 2022;28(6):925-932. doi:10.1177/13524585211047223
  3. ENSPRYNG® (satralizumab-mgwe) [prescribing information] Genentech, Inc. 
  4.  SOLIRIS® (eculizumab) [prescribing information] Alexion Pharmaceuticals, Inc.
  5. Cree BAC, Bennett JL, Kim HJ, et al. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD. Mult Scler. 2021;27(13):2052-2061. doi:10.1177/1352458521988926
  6. Data on File. Horizon, June 2020.
  7. UPLIZNA (inebilizumab-cdon) [prescribing information] Horizon.
  8.  Aktas O, Bennett JL, Weinshenker 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: The 16th World Congress on Controversies in Neurology (virtual); March 24-27, 2022.
  9. 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