WO2022006283A2 - Methods of treating neuromyelitis optica spectrum disorder - Google Patents

Methods of treating neuromyelitis optica spectrum disorder Download PDF

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Publication number
WO2022006283A2
WO2022006283A2 PCT/US2021/039911 US2021039911W WO2022006283A2 WO 2022006283 A2 WO2022006283 A2 WO 2022006283A2 US 2021039911 W US2021039911 W US 2021039911W WO 2022006283 A2 WO2022006283 A2 WO 2022006283A2
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subject
nmosd
sgfap
need
administering
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English (en)
French (fr)
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WO2022006283A3 (en
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William Rees
Eliezer Katz
Michael Smith
Nanette MITTEREDER
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Viela Bio Inc
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Viela Bio Inc
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Priority to KR1020237002980A priority Critical patent/KR20230030642A/ko
Priority to AU2021299307A priority patent/AU2021299307A1/en
Priority to CA3178954A priority patent/CA3178954A1/en
Priority to JP2022581408A priority patent/JP2023534916A/ja
Priority to IL299381A priority patent/IL299381A/en
Priority to BR112022026747A priority patent/BR112022026747A2/pt
Priority to EP21834411.7A priority patent/EP4172211A4/en
Priority to CN202180046409.5A priority patent/CN116234571A/zh
Application filed by Viela Bio Inc filed Critical Viela Bio Inc
Priority to MX2022016236A priority patent/MX2022016236A/es
Publication of WO2022006283A2 publication Critical patent/WO2022006283A2/en
Publication of WO2022006283A3 publication Critical patent/WO2022006283A3/en
Priority to US18/147,287 priority patent/US20230406928A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Definitions

  • Neuromyelitis Optica Spectrum Disorder is a rare, chronic, autoimmune, inflammatory disorder of the central nervous system (Cree BA, et al., Mult Sc!er. 2016;22(7):862-872). It is typically characterized by recurrent attacks of optic neuritis and longitudinally extensive transverse myelitis, while brain and brainstem inflammation are less frequently observed. Attacks can be severe, and recovery is typically incomplete, thus leading to cumulative disability.
  • immunosuppressants such as corticosteroids and mycophenolate mofetil (Trebst C, eta!., J Neurol 2014;261(1): 1-16), and rituximab, a CD20 B-cell-depleting antibody (Cree BA, et al, Neurology. 2005:64(7): 1270-1272; Damato V, et al, JAMA Neurol, 2016;73(11 ): 1342-1348), are used as maintenance therapeutics to prevent attacks, although clinical evidence for their effectiveness is limited and based on uncontrolled or retrospective studies. A number of new therapies have recently proved to be effective (Pittock SJ, et al., N Engl J Med.
  • inebiiizumab a humanized affinity-optimized, afucosylated immunoglobulin G1 kappa monoclonal antibody (Chen D, et. al., J Clin Med., 2016;5(12); Cree B, et al., Lancet, 2019;394(10206):1352-1363).
  • Inebilizumab binds to the B-cell-specific surface antigen CD19 and depletes a wide range of B cells.
  • NMODS-related damage reducing neuromyelitis optica spectrum disorder (NMOSD) ⁇ related damage in a subject in need thereof, comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject in need thereof, thereby reducing the NMODS-related damage, wherein the subject in need thereof comprises a serum glial fibrillary astrocytic protein (sGFAP) concentration of at least about 160 pg/mL.
  • sGFAP serum glial fibrillary astrocytic protein
  • the sGFAP concentration is at least about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/ ' rnL, or about 173 pg/mL or greater. In aspects, the sGFAP concentration is at least about 170 pg/mL.
  • the composition that comprises Inebilizumab or the derivative thereof is administered intravenously. In aspects, the intravenous administration is at a dose of about 300 mg. In aspects, the administering is repeated at least twice.
  • the administering is repeated every 6 months.
  • the reducing NMOSD-related damage is determined by at least one of: (a) a reduction in a number of NMOSD-related attacks in the subject in need thereof after the administering as compared to a baseline number of NMOSD-related attacks in the subject in need thereof before the administering; or (b) a reduction in a number of NMOSD-related attacks in the subject in need thereof after the administering as compared to an otherwise comparable control subject lacking the administering.
  • the baseline number of NMQDS-related attacks are determined over a first time period preceding the administering, wherein the number of NMQDS-related attacks reduced by the administering are determined over a second time period following the administering, and wherein the first time period and the second time period are of equal length.
  • the first time period and the second time period are at least one year.
  • the reducing the NMOSD-related damage comprises reducing NMOSD-related attacks that are graded major in severity in the subject in need thereof.
  • the reducing the NMOSD-related damage comprises eliminating NM08D- related attacks that, are graded major in severity in the subject in need thereof.
  • the reducing the NMOSD-related damage in the subject in need thereof comprises: (a) reducing a number of magnetic resonance imaging (MRI) lesions; (b) reducing rate of increase in new MRI lesions; or (c) both (a) and (b).
  • the reducing the NMOSD-related damage in the subject in need thereof comprises: (a) reducing a rate of worsening of expanded disability status scale (EDSS) score; or (b) improving the EDSS score.
  • the methods further comprise identifying the subject in need thereof by determining the sGFAP concentration of at least about 160 pg/mL.
  • NMODS neuromyelitis optica spectrum disorder
  • the sGFAP concentration is about: 166 pg/mL, 167 pg/mL, 168 pg/mL, 169 pg/mL, 170 pg/mL, 171 pg/mL, 172 pg/mL, 173 pg/mL, or greater. In aspects, the sGFAP concentration is about 170 pg/mL.
  • the composition that comprises Inebilizumab or the derivative thereof is administered intravenously. In aspects, the intravenous administration is at a dose of about 300 mg. In aspects, the administering is repeated at least twice. In aspects, the administering is repeated every 6 months.
  • the preventing lasts for at least 1 year after the administering. In aspects, the preventing lasts for at least 2 years after the administering. In aspects, the administering decreases sGFAP concentration: (a) in the subject in need thereof as compared to sGFAP concentration prior to the administering; (b) in the subject in need thereof as compared to the subject in need thereof s baseline sGFAP concentration; or (c) in an otherwise comparable subject in need thereof lacking the administering. In aspects, the preventing results in a reduction in MRI lesions in the subject in need thereof as determined by: (a) a reduction in a number of the MR lesions; (b) a reduction in size of the MM lesions; or (c ) both (a) and (b). In aspects, the preventing results in an improvement in EDSS score in the subject in need thereof.
  • NMOSD neuromyelitis optica spectrum disorder
  • identifying the subject as at-risk for an NMOSD-related attack wherein the subject is identified as an at-risk subject if the subject comprises an increase in sGFAP concentration relative to a baseline sGFAP concentration; and (b) administering a therapeutic to the at-risk subject in an amount effective to suppress the NMODS-related attack, wherein the administering is performed at most one week following the identifying.
  • the increase in the sGFAP concentration comprises an at least 10-fold increase relative to the baseline sGFAP concentration.
  • the increase in the sGFAP concentration comprises an at least 20-fold increase relative to the baseline sGFAP concentration.
  • the subject at risk for the NMOSD-related attack is not undergoing a treatment for NMQSD that comprises Inebiiizumab or a derivative thereof.
  • the increase in sGFAP concentration comprises an increase of 50% to 150% relative to the baseline sGFAP concentration; wherein the subject at risk for the NMOSD-related attack is undergoing treatment for NMOSD, and wherein the treatment comprises Inebiiizumab or a derivative thereof.
  • the therapeutic comprises one or more of a steroid, plasmapheresis, immunoadsorption, or a complement inhibitor.
  • the therapeutic comprises one or more of Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, Azathioprine, Mycophenolate Mofetil, or a low dose corticosteroid.
  • the administering is performed at most 24 hours following the identifying.
  • the suppressing the NMOSD-related attack comprises: (a) reducing a number of NMODS-related attacks; or (b) preventing a NMOSD-related attack.
  • the methods comprise (a), wherein the reducing comprises reducing a number of NMODS-related attacks graded as major in severity.
  • the suppressing the NMOSD-related attack comprises a recovery from the NMOSD-related attack that is graded as a major recovery. In aspects, the suppressing the NMOSD-related attack results in a prevention of new MRI lesions in the subject at-risk for an NMOSD-related attack. In aspects, the suppressing the NMOSD-related attack results in a reduction in NMOSD-related disability in the subject at-risk for an NMOSD-related attack. In aspects, the reduction in NMOSD-related disability' is a reduction in worsening of the subject at-risk for an NMOSD-related attack’s EDSS score. In aspects, the therapeutic comprises Inebiiizumab or a derivative thereof.
  • sGFAP serum glial fibrillar ⁇ ' acidic protein
  • the sGFAP concentration is about: 165 pg/mL, 166 pg/mL, 167 pg/rnL, 168 pg/mL, 169 pg/mL, 170 pg/mL, 171 pg/mL, 172 pg/mL, 173 pg/mL, or greater.
  • the subject in need thereof has a sGFAP concentration of about 170 pg/mL to 171 pg/mL.
  • the B cell depleting therapy comprises Inebilizumab or a derivative thereof.
  • the therapeutically effective amount of the B cell depleting therapy is about 300 mg.
  • NMOSD neuromyelitis optica spectrum disorder
  • the methods comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject in need thereof, thereby reducing the NMQSD-related disability, wherein the subject in need thereof comprises: (a) an increase in serum Neurofilament light chain (sNfL) levels over a baseline level of the subject in need thereof; or (b) an increase in sNfL levels over an otherwise comparable control subject.
  • the methods further comprise identifying the subject in need thereof.
  • NMOSD neuromyelitis optica spectrum disorder
  • methods of reducing neuromyelitis optica spectrum disorder (NMOSD)- related disability in a subject diagnosed with NMOSD comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject diagnosed with NMQDS, wherein the subject diagnosed with NMQDS comprises: (a) an increase in serumNeurofilament light chain (sNfL) level over a baseline level of the subject diagnosed with NMQDS; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • sNfL serumNeurofilament light chain
  • NMOSD neuromyelitis optica spectrum disorder
  • methods of treating neuromyelitis optica spectrum disorder comprising: (a) identifying a subject in need thereof at increased risk for NMQSD-related disability as determined by: (i) an increased serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof; or (ii) an increased sNfL level over an otherwise comparable control subject; and (b) administering a composition that comprises Inebilizumab or a derivative thereof to the subject identified in (a), thereby treating the NMQDS,
  • sNfL serum Neurofilament light chain
  • NMOSD neuromyelitis optica spectrum disorder
  • the methods comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject, in need thereof, thereby treating the NMQDS, wherein the subject in need thereof comprises: an increased serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof, or (b) an increased sNfL level over an otherwise comparable control subject.
  • the subject in need thereof comprises about 1.0, about 1.1, about 1.2, about 1.3, about 1,4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0 or greater fold change in serum Nil over a baseline level.
  • the subject in need thereof has a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL or greater.
  • NMOSD neuromyelitis optica spectrum disorder
  • methods of treating a subject suspected of having neuromyelitis optica spectrum disorder comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject, wherein the subject comprises one or more NMQDS-refated symptoms and at least one of: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • sNfL serum Neurofilament light chain
  • NMOSD-related diseases comprising: (a) identifying a subject as having one or more NMOSD-related symptoms; (b) determining if the subject identified in (a) is at increased risk for NMOSD-related disability as determined by (i) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject identified in (a); or (ii) an increase in sNfL levels over an otherwise comparable control subject; and (c) administering a composition that comprises Inebilizumab or a derivative thereof to the subject determined to be at increased risk for NMOSD-related disability from (b).
  • NMOSD-related symptoms comprising: (a) identifying a subject as having one or more NMOSD-related symptoms; (b) determining if the subject identified in (a) is at increased risk for NMOSD-related disability as determined by (i) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject identified in (a); or (ii) an increase in
  • NMODS neuromyelitis optica spectrum disorder
  • the methods comprising administering a therapeutic in an amount effective to treat the NMODS in the subject in need thereof, wherein the subject in need thereof comprises: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • sNfL serum Neurofilament light chain
  • NMOSD neuromyelitis optica spectrum disorder
  • methods of treating a subject suspected of having neuromyelitis optica spectrum disorder comprising administering a therapeutic to the subject suspected of having NMOSD, wherein the subject suspected of having NMOSD comprises one or more NMODS-related symptoms and at least one of: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject suspected of having NMOSD, or (b) an increase in sNfL level over an otherwise comparable control subject.
  • sNfL serum Neurofilament light chain
  • the therapeutic comprises one or more of Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, Azatbioprine, Mycophenolate Mofetil, or a low' dose corticosteroid.
  • the present disclosure provides methods of reducing NMOSD-related damage in a subject at increased risk therefor. In the methods, a subject is identified as at increased risk for NMOSD-related damage.
  • the subject is identified as at increased risk for NMOSD-related damage if the subject comprises a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL or greater.
  • VIB551 is intravenously administered to the at increased risk subject to reduce the NMOSD-related damage.
  • the subject is identified as at increased risk if the subject comprises a sGFAP concentration of about 170 pg/mL or greater.
  • the VIB551 is administered intravenously at a dose of 300 mg every 6 months.
  • reducing NMOSD-related damage comprises reducing number of NMOSD-related attacks in the at increased risk subject relative to a baseline number of NMOSD-related attacks in the at increased risk subject, wherein the baseline number of attacks are determined over a first time period preceding the administering VIB551, wherein the number of attacks reduced by the administering VIB551 are determined over a second time period following the administering VIB551, and wherein the first and the second time period are of equal length.
  • the first and the second time period are at least one year.
  • reducing the NMOSD-related damage comprises reducing likelihood of NMOSD-related attacks in the at increased risk subject graded major in severity.
  • reducing the NMOSD-related damage comprises preventing NMOSD-related attacks in the at increased risk subject graded major in severity.
  • reducing the NMOSD-related damage comprises reducing number of magnetic resonance imaging (MRI) lesions or reducing rate of increase in new MRI lesions in the at increased risk subject.
  • the reducing the NMOSD-related damage comprises reducing rate of worsening of expanded disability status scale (EDSS) score, or improving EDSS score, of the at increased risk subject.
  • EDSS expanded disability status scale
  • the disclosure also provides methods of preventing or reducing the likelihood of NMQSD relapse in a subject diagnosed with NMOSD.
  • a subject is identified as a subject for preventing NMOSD relapse.
  • the subject is identified as a subject for preventing NMOSD relapse if the subject comprises a sGFAP concentration of less than about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/m L, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, about 173 pg/mL, about 174 pg/mL, about 175 pg/mL, about 176 pg/mL, or about 181 pg/mL.
  • VIB551 is administered to the subject identified as a subject to prevent or reduce the likelihood of NMOSD relapse.
  • the subject is identified as a subject if the subject comprises a sGFAP concentration of less than about 170 pg/mL.
  • the VTB551 is administered intravenously at a dose of 300 mg every 6 months.
  • preventing comprises a time period of at least 1 year.
  • administering decreases sGFAP concentration in the subject relative to baseline sGFAP concentration or as compared to sGFAP in a control subject, and wherein the preventing comprises a time period of at least 2 years.
  • preventing results in a reduction in MRI lesions in the subject.
  • preventing results in an improvement in EDSS score in the subject.
  • the disclosure further provides for methods of suppressing a NMOSD-related attack in a subject diagnosed with NMOSD.
  • the subject is identified as at-risk for an NMOSD-related attack.
  • the subject is identified as at-risk for an NMOSD-related attack if the subject’s sGFAP concentration has increased relative to baseline sGFAP concentration of the subject or as compared to a control subject.
  • a therapeutic is administered to the at- risk subject at most one week following the identification to suppress the NMOSD-related attack.
  • the increase in sGFAP concentration comprises an at least 10-fold increase; and wherein the at-risk subject is not undergoing a treatment for NMOSD that comprises VIB551.
  • the increase in sGFAP concentration comprises an atleast 20-fold increase; and wherein the at-risk subject is not undergoing a treatment for NMOSD that comprises VIB551.
  • the increase in sGFAP concentration comprises an increase of 50% to 150%; and wherein the at-risk subject is undergoing treatment for NMOSD, wherein the treatment comprises VIB551.
  • the therapy comprises one or more of steroids, plasmapheresis, immunoadsorption or a complement inhibitor.
  • the treatment comprises one or more of Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, azathioprine, my cophenol ate mofetil or low dose corticosteroids.
  • the administering is performed at most 24 hours following the identifying,
  • suppressing the NMOSD-related attack comprises reducing likelihood of or preventing the NMOSD-related attack.
  • suppressing the NMOSD-related atack comprises reducing likelihood of or preventing the NMOSD-related attack from being graded as major in severity.
  • suppressing the NMOSD-related atack comprises a recovery from the NMOSD-related attack that is graded as a major recovery.
  • suppressing the NMOSD-related attack results in a prevention of new MRI lesions in the at- risk subject.
  • suppressing the NMOSD-related attack results in a reduction in NMOSD-related disability in the at-risk subject.
  • the reduction in NMOSD- related disability is a reduction in worsening of the at-risk subject’s EDSS score.
  • the therapy comprises VTB551.
  • the disclosure also provides for methods of treating NMOSD in a subject.
  • a therapeutically effective amount of a B cell depleting therapy is administered to the subject when the subject has a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL or greater.
  • the subject has a sGFAP concentration of about 170 pg/mL to 171 pg/mL.
  • the B cell depleting therapy is VIB551 and the therapeutically effective amount comprises a dose of 300 mg.
  • the disclosure also provides methods of reducing NMOSD-reiated disability in a subject diagnosed with NMOSD, the methods comprising: identifying a subject as at increased risk for NMOSD-related disability, wherein the subject is identified as at increased risk if the subject has an increase in serum Neurofilament light chain (NfL) levels over a baseline level: and administering VIB551 to the subject.
  • NfL serum Neurofilament light chain
  • the disclosure also provides methods of reducing NMOSD-reiated disability in a subject diagnosed with NMOSD, the methods comprising administering VIB551 to a subject with an increase in serum Nfl levels over a baseline level of the subject or as compared to serum Nfl levels of a control subject.
  • the disclosure also provides methods of treating NMOSD in a subject, the methods comprising: identifying a subject as at increased risk for NMOSD-reiated disability, wherein the subject is identified as at increased risk if the subject has an increase in serumNeurofilament light chain (NfL ) levels over a baseline level; and administering VIB551 to the subject.
  • the disclosure also provides methods of treating NMOSD in a subject, the methods comprising administering VIB551 to a subject with an increase in serum Nfl levels over a baseline level.
  • the subject has an about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0 or greater fold change in serum Nfl over baseline levels.
  • the subject has a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL, or greater.
  • the disclosure also provides methods of treating a subject suspected of having NMOSD, the methods comprising administering VIB551 to a subject with an increase in serum Nfl levels over a baseline level.
  • the subject also comprises one or more NMOSD- reiated symptoms.
  • the disclosure also provides methods of treating a subject suspected of having NMOSD, the methods comprising: identifying a subject as having one or more NMOSD- reiated symptoms; identifying a subject as at increased risk for NMOSD-reiated disability, wherein the subject is identified as at increased risk if the subject has an increase in serum Neurofilament light chain (NfL) levels over a baseline level; and administering VIB55I to the subject.
  • NfL serum Neurofilament light chain
  • the disclosure also provides methods of treating NMOSD in a subject, the methods comprising a administering a therapeutic to a subject with an increase in serum Nfl levels over a baseline level.
  • the disclosure also provides methods of treating a subject suspected of having NMOSD, the methods comprising administering a therapeutic to a subject with an increase in serum Nfl levels over a baseline level and one or more NMOSD-related symptoms.
  • the therapeutic comprises one or more of Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, azathioprine, mycophenolate mofetil or low dose corticosteroids .
  • Fig, 1 is an exemplary Consolidated Standards of Reporting Trials (CONSORT) flow diagram for the N-MOmentum study participants.
  • FIG. 2A provides a graph showing baseline sGFAP concentration in each of the NMOSD, relapsing-remitting multiple sclerosis (RRMS), and Healthy Donor (HD) cohorts; dashed line represents 2 standard deviations from the HD mean (170 pg/mL); box and whiskers represent sample quartiles; statistical significance of differences in sGFAP concentration between groups was assessed using the Mann--- Whitney U test.
  • 2B provides baseline sGFAP for healthy donors, RRMS subjects and NMOSD subjects by serostatus according to whether they were aquaporin 4-immunoglobulin G seropositive (AQP4+), aquaporin 4-immunoglobulin G seronegative (AQP4-), myelin oligodendrocyte glycoprotein- immunoglobulin G seropositive (MOG+-), or both AQP4---/MOG- (double negative; “DN”). Box and whiskers represent sample quartiles.
  • FIG. 3A provides baseline sGFAP for healthy donors according to age.
  • Fig, 3R provides baseline sGFAP for subjects with NMODS according to age.
  • Fig. 3C provides baseline sGFAP for healthy donors according to gender.
  • Fig. 3D provides baseline sGFAP for subjects with NMODS according to gender.
  • Fig. 3E provides baseline sGFAP for healthy donors according to ethnicity.
  • Fig, 3F provides baseline sGFAP for healthy donors according to ethnicity.
  • FIG. 4A provides a graph showing Kaplan -Meier plots of time until first NMQSD attack, i.e., attack-free survival, for all NMQSD trial participants according to whether their baseline sGFAP was elevated.
  • Fig, 4B shows a Kaplan-Meier plot of time until first NMQSD attack, i.e., attack-free survival, during the RCP for NMOSD trial participants with (> 170 pg/mL) or without ( ⁇ 170 pg/mL) an elevated baseline sGFAP concentration who received placebo.
  • FIG. 4C shows a Kapian-Meier plot of time until first NMOSD attack, i.e., attack-free survival, during the RCP for NMQSD trial participants with (> 170 pg/mL) or without ( ⁇ 170 pg/mL) an elevated baseline sGFAP concentration who were administered Inebilizumab.
  • first NMOSD attack i.e., attack-free survival
  • NMQSD trial participants with (> 170 pg/mL) or without ( ⁇ 170 pg/mL) an elevated baseline sGFAP concentration who were administered Inebilizumab.
  • FIG. 4D shows a Kapian-Meier plot of time until first NMQSD attack, i.e., atack-free survival, in NMOSD trial participants who received placebo or Inebilizumab with > 170 pg/mL elevated baseline sGFAP concentration.
  • Fig. 4E shows a Kapian-Meier plot of time until first NMOSD attack, i.e., atack-free survival, in NMQSD trial participants who received placebo or Inebilizumab with ⁇ 170 pg/mL elevated baseline sGFAP concentration.
  • FIG. 5A provides a graph showing a profile plot of sGFAP concentration measurements taken at baseline and at visits leading to an adjudicated NMOSD attack for each of 37 NMOSD trial participants who had both experienced an adjudicated attack and provided sGFAP measurements; overall, 29/37 (78%) samples were above the healthy donor range of 170 pg/mL.
  • Fig. 5B provides baseline sGFAP levels and sGFAP levels of NMQSD trial participants who experienced an adjudicated attack in each of the four weeks leading up to, and at the approximate time of, an NMOSD-related attack.
  • Fig. 5A provides a graph showing a profile plot of sGFAP concentration measurements taken at baseline and at visits leading to an adjudicated NMOSD attack for each of 37 NMOSD trial participants who had both experienced an adjudicated attack and provided sGFAP measurements; overall, 29/37 (78%) samples were above the healthy donor range of 170 pg/mL.
  • Fig. 5B provides baseline sGFAP
  • SC provides sGFAP concentration (pg/mL) during an adjudicated attack in trial participants who were AQP4+ and placebo-treated, AQP4+ and VIB 551 -treated, AQP4- MOG and VIB551 -treated, and DN and VIB551 -treated.
  • Fig, 5D provides the fold change in baseline sGFAP during an adjudicated attack in trial participants who were AQP4+ and placebo-treated, AQP4+ and VIB551 -treated, AQP4- MOG+ and VIB551 -treated, and DN and VIB551 -treated.
  • Fig. 6A shows sGFAP concentration within 1 week of (before or after) an ad j udicated NMOSD attack by attack severity. Attack severity was measured by the opticospinal impairment scale.
  • Fig. 6B shows sGFAP concentration within 1 week of (before or after) an adjudicated NMQSD attack by domain involvement. Of the attacks across multiple domains, 4 were minor myelitis attacks, and 1 sample from myelitis major attack group displayed sGFAP within the healthy donor range. Box and whiskers represent sample quantiles. Statistical significance between groups was assessed using Mann-Whitney U test. Dotted line in each graph represents the border of the healthy donor range of 170 pg/mL sGFAP; **P ⁇ .01; ***P ⁇ .001; ns, not significant.
  • Figures 7 A -- 7D sGFAP concentration predicts attack severity in both placebo and Inebilzumab treated participants.
  • Fig, 7.4 provides a boxplot of sGFAP concentrations for placebo-treated trial participants within 1 week of an adjudicated NMOSD attack, split by attack severity.
  • Fig. 7B provides a boxplot of sGFAP concentrations for placebo-treated trial participants within 1 week of an adjudicated NMOSD attack, split by domain involvement.
  • Fig. 7C provides a boxplot of sGFAP concentrations for Inebilizumab-treated trial participants within 1 week of an adjudicated NMOSD attack, split by attack severity.
  • FIG. 8A shows sGFAP concentration during adjudicated NMOSD attacks in placebo-treated participants; statistical significance of increases from baseline was assessed using the Wilcoxon signed-rank test.
  • Fig. 8B shows sGFAP concentration during adjudicated NMOSD attacks in Inebilizumab-treated participants; statistical significance of increases from baseline was assessed using the Wilcoxon signed-rank test.
  • Fig. 8A shows sGFAP concentration during adjudicated NMOSD attacks in placebo-treated participants; statistical significance of increases from baseline was assessed using the Wilcoxon signed-rank test.
  • Fig. 8B shows sGFAP concentration during adjudicated NMOSD attacks in Inebilizumab-treated participants; statistical significance of increases from baseline was assessed using the Wilcoxon signed-rank test.
  • Fig. 8D provides a bar graph to show the proportion of samples from placebo- and, separately, Inebilizumab- treated subjects with elevated sGFAP concentrations (> 171 pg/mL) by the end of the RCP.
  • Figures 9A - 9E demonstrate that in NMOSD subjects who do not experience an adjudicated attack, increased sGFAP signaled increased NMOSD-related disease activity.
  • Fig, 9.4 provides a profile plot of longitudinal fold change from baseline in sGFAP in subjects with NMQSD who experienced adjudicated attacks (light gray), those who did not experience adjudicated attacks but displayed an increase greater than twofold from baseline (dark gray), and in those who neither experienced attacks nor displayed increases greater than twofold from baseline (mid gray) in sGFAP during the RCP.
  • Fig. 9B provides boxplots displaying sGFAP concentrations observed in 10 healthy donor (HD) subjects across three blood draws.
  • FIG. 9C provides the proportion of new spinal cord T2 lesions observed in subjects who did not experience adjudication committee (AC)-adjudicated attacks, but either did or did not display a greater than twofold (FC) increase in sGFAP during the RCP.
  • Fig. 9D provides the proportion of subjects with new Gd positive Tl lesions observed in subjects who did not experience adjudication committee (AC)-adjudicated attacks, but either did or did not display a greater than twofold (FC) increase in sGFAP during the RCP.
  • Fig. 9E provides a graph showing proportion of participants with an increase greater than two-fold in sGFAP from baseline. Statistical significance in the between-group difference was assessed using the Cochran-Armitage test.
  • Fig. 10A provides VIB55Fs VH (SEQ ID NO:1) amino acid sequence and Fig. 10B provides VIB551’s VL (SEQ ID NO: 2) amino acid sequence.
  • the amino acid sequence of each of VIB551s VH CDRl (SEQ ID NO: 3), VH CDR2 (SEQ ID NO:4), VH CDR3 (SEQ ID NO: 5), VL CDRl (SEQ ID NO:6), VL CDR2 (SEQ ID NO:7) and VL CDR3 (SEQ ID NO:8) is separately indicated within its respective VH and VL amino acid sequence.
  • Fig, 11 shows the disposition, demographics and baseline characteristics of the AQP4- IgG seropositive vs. AQP4-IgG seronegative subgroup of the N-M Omen turn study.
  • 1 subject (AQP4-IgG seronegative) was randomized to Inebilizumab but did not receive treatment.
  • Fig, 12 shows the NMQSD attacks during the RCP for AQP4-IgG seronegative subjects.
  • AC adjudication committee
  • AQP4 aquaporin-4
  • Gd+ Gadolinium- enhancing, IgG, immunoglobulin G, IgG 1..
  • immunoglobulin G1; MOG myelin oligodendrocyte glycoprotein; NMO/NMOSD, neuromyelitis optica/ neuromyelitis optica spectrum disorder; ON, optic nerve; RCP, randomized-controlled period.
  • Fig. 13 shows the annualized attack rates during RCP (post hoc analysis) for AQP4- IgG seronegative subjects.
  • Fig. 14 shows the annualized attack rates during OLE for for AQP4 ⁇ IgG seronegative subjects.
  • Figures 1SA - 15D Demonstrate that biomarkers of neuronal injury were elevated in subjects with NMOSD.
  • Fig. 15A shows increased levels of sGFAP in NMOSD subjects as compared to HC and RRMS.
  • Fig. 15B shows increased levels of sNfl in NMOSD subjects as compared to HC and RRMS.
  • Fig. 15C shows increased levels of sUCHLl in NMOSD subjects as compared to HC and RRMS.
  • Fig. 15D shows increased levels of sTau in NMOSD subjects as compared to HC and RRMS.
  • HC healthy control
  • NMOSD neuromyelitis optica spectrum disorder
  • sGFAP serum glial fibrillary acidic protein
  • sNfL soluble neurofilament light chain
  • sUCH-Ll soluble ubiquitin carboxyl-terminal hydrolase L1.
  • Figures 16A-16D Demonstrate that the NMOSD attacks increased biomarker levels.
  • Fig. 16A shows median Fc change from baseline in sGFAP in placebo-treated or Inebilizumab- treated subjects.
  • Fig. 16B shows median Fc change from baseline in sNfl in placebo-treated or Inebilizumab-treated subjects.
  • Fig. 16C shows median Fc change from baseline in sTau in placebo-treated or Inebilizumab-treated subjects.
  • Fig. 16D shows median Fc change from baseline in sUCHL1 in placebo-treated or Inebilizumab-treated subjects.
  • FC fold change
  • NMOSD neuromyelitis optica spectrum disorder
  • sGFAP serum glial fibrillary acidic protein
  • sNfL soluble neurofiiament light chain
  • sUCH-L soluble ubiquitin carboxyl- terminal hydrolase LI.
  • Figures 17A-17D Demonstrate that baseline elevations in biomarkers were significantly correlated with increased attack risk.
  • Fig. 17.4 shows percent of subjects that are attack free as a function of time and sGFAP status.
  • Fig. 17B shows percent of subjects that are attack free as a function of time and sNfl status.
  • Fig. 17C shows percent of subjects that are attack free as a function of time and sTau status.
  • Fig. 17D shows percent of subjects that are attack free as a function of time and sUCHLl status.
  • Fig. 18 Provides a sGFAP baseline-controlled regression analysis demonstrated that biomarkers other than sGFAP were not independently associated with atack risk.
  • NMOSD neuromyelitis optica spectrum disorder
  • sGFAP serum glial fibrillary' acidic protein
  • sNfL soluble neurofiiament light chain
  • sUCH-L1 soluble ubiquitin carboxyl-terminal hydrolase
  • Fig. 19 Demonstrates that sNfL at atack is strongest correlate of EDSS change at attack follow-up.
  • the term “about” or “approximately” when immediately preceding a numerical value means a range plus or minus 10% of that value.
  • “about 50” can mean 45 to 55
  • “about 25,000” can mean 22,500 to 27,500, etc., unl ess the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation.
  • “about 49, about 50, about 55, . . “about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 52.5.
  • the phrases “less than about” a value or “greater than about” a value should be understood in view' of the definition of the term “about” provided herein.
  • identity is used to denote similarity between two sequences. Unless otherwise indicated, percent identities described herein are determined using the BLAST algorithm available at the world wide web address: blast.ncbi.nlm.nih.gov/Blast.cgi using default parameters.
  • compositions and methods of use thereof for the treatment or prevention of Neuromyelitis Optica Spectrum Disorder (NMOSD) and associated disabilities and symptoms are also methods of reducing NMOSD -related damage in a subject at increased risk therefor, preventing NMOSD relapse in a subject diagnosed with NMOSD, suppressing an NMOSD-related attack in a subject diagnosed with NMOSD, and treating NMOSD in a subject.
  • serum glial fibrillary acidic protein (sGFAP) concentration can he useful in identifying: a subject in need thereof, a subject in need of treatment for NMOSD, or a subject in need of an adjustment in treatment for NMOSD.
  • increases in serum Neurofilament light (Nil) levels over baseline levels may be used to identify subjects at increased risk for NMOSD-related disability.
  • the subject is AQP4-IgG seronegative.
  • the subject is AQP4-IgG seropositive.
  • compositions that comprise Inebilizumab or a derivative thereof may be administered in any of the methods, including but not limited to, methods of treating NMOSD, described herein. For example, if the subject is identified as at increased risk for NMQSD-related damage, or if the subject is identified as a subject for preventing or reducing the likelihood of NMOSD relapse, Inebiiizumab or a derivative thereof may be administered to the subject, and the administration of Inebiiizumab or the derivative thereof may he intravenously at a dose of 300 mg every six months.
  • VIB551 is a humanized antibody with a VH amino acid sequence and a YL amino acid sequence as shown in Fig.
  • VIB551 may also be referred to as MEDI551, Inebiiizumab or UPLIZNATM. VIB551 and methods of making thereof are described in International PCX Patent Application PCT/US2007/077916, published as WO 2008/031056, which is hereby incorporated by reference (PCT/U S2007/077916 refers to VIB551 as “16C4”). In aspects, VIB551 (also referred to HZN551, MEDI551, UPLIZNATM or Inebulizumab; disclosed in U .S. Appl. No. 11/852,106 and Int’l Appl. No.
  • a derivative of VIB551 includes but is not limited to an antibody with the VH amino acid sequence and the VL amino acid sequence as shown in Fig. 10A and Fig. 10B, but for one or more substitutions in amino acid residues that do not alter the function of VIB551.
  • a VIB551 derivative is an antibody with the VH amino acid sequence and the VL amino acid sequence as shown in Fig. 10A or Fig, HOB, with 1, 2, 3, 4, or 5 amino acid residue substitutions and/or deletions.
  • a derivative of Inebiiizumab includes the same CDR amino acid sequences as the VH and the VL, sequences as shown in Fig. 10.4 or Fig, 10B, but may have one or more amino acid substitutions in the framework regions of the VH and the VL sequences shown in Fig. 10A or Fig. 10B.
  • Inebiiizumab, a portion thereof, or a derivative thereof comprises at least about or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or up to about 99% identity' with any one of SEQ ID NO: 1 - SEQ ID NO: 10.
  • a VH of Inebiiizumab corresponds to SEQ ID NO:l .
  • a VL of Inebilizumab corresponds to SEQ) ID NO:2.
  • the amino acid sequence of each of Inebilizumab’s VH CDR1 (SEQ ID NQ:3), VH CDR2 (SEQ ID NO:4), VH CDR3 (SEQ ID NO: 5), VL CDRl (SEQ ID NO:6), VL CDR2 (SEQ ID NO: 7) and VL CDR3 (SEQ ID NO: 8) correspond to each of the aforementioned sequences.
  • Inebilizum ab may comprise a heavy chain comprising the amino acid of SEQ ID NO:9 and a light chain comprising the amino acid of SEQ ID NO: 10.
  • Inebilizumab may have the heavy chain amino acid sequence of SEQ ID NO:9 and the light chain amino acid sequence of SEQ ID NO: 10 but for one or more changes in amino acid residues that do not alter the function of Inebilizumab.
  • the number of amino acid changes may be 1 amino acid residue change, 2 amino acid residue changes, 3 amino acid residue changes, 4 amino acid residue changes, or 5 amino acid residue changes.
  • a sequence of SEQ ID NO: I- SEQ ID NO: 10 comprises an amino acid residue insertion, deletion, or modification of 0-10, 0-2, 0-5, 0-3, or 1-5 residues.
  • a sequence of SEQ) ID NO: 1- SEQ ID NO: 10 comprises an amino acid residue insertion, deletion, or modification of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 residues.
  • the administration of a compositions that comprises Inebilizumab or a derivative thereof in the methods described herein may be every ' 6 months or approximately 6 months.
  • the administration of Inebilizumab or the derivative thereof may be every 6 months, every 180 days, between about every 170 and about every 190 days, between about every 175 and about every 185 days, between about every 175 and about every 190 days, or between about every' 170 and about every 185 days.
  • the administration of Inebilizumab or the derivative thereof may be about every' 26 weeks, about every 25 weeks, about every 27 weeks, between about every' 25 and about every 27 weeks, between about every 25 and about even' 26 weeks, or between about every' 26 and about every 27 weeks.
  • an initial Inebilizumab or derivative of Inebilizumab dose may be administered to the subject. If an initial dose is administered, the initial dose may be administered approximately 2 weeks before the approximately even 6-month dosing. The administering of the initial dose approximately 2 weeks before the even approximately 6- month dosing may be the administering of the initial dose 12 days, 13 days, 14 days, 15 days, or 16 days before the approximately every 6 months dosing. The initial dose may or may not be co-administered with oral corticosteroids.
  • the dose of Inebilizumab or the derivative thereof administered intravenously in the methods described herein may be 300 mg or approximately 300 mg.
  • An approximately 300 mg dose may be a dose of about 250 mg to about 350 mg, it may be a dose of about 275 mg to about 325 mg, it may be a dose of about 290 mg to about 310 mg, it may be a dose of about 205 mg to about 305 mg, or it may be a dose of 275 mg, 280 mg, 285 mg, 290 mg, 295 mg, 300 mg, 305 mg, 310 mg, 315 mg, 320 mg, or 325 mg.
  • an alternative therapeutically acceptable NMQSD agent may be administered to the subject in place of Inebilizumab or a derivative thereof, e.g., administered to the subject identified as at increased risk for NMOSD-related damage or identified as a subject for preventing or reducing the likelihood of NMOSD relapse.
  • An alternative therapeutically acceptable NMOSD agent may be a B cell depleting therapy other than Inebilizumab, such as CD 19 antibody, e.g., MOR00208 (also referred to as Xmab 5574 or tafasitamab; disclosed in U.S. Patent Application No. 20170137516), an anti-CD20 antibody, e.g., Rituximab (antibody C2B8 in WO94/11026), Ocrelizim ab (also referred to as Oerevus® or PRO70769; disclosed in Vugmeyster, Y., et al., J. Immunother.
  • CD 19 antibody e.g., MOR00208 (also referred to as Xmab 5574 or tafasitamab; disclosed in U.S. Patent Application No. 20170137516)
  • an anti-CD20 antibody e.g., Rituximab (antibody C2B8 in WO94/11026)
  • an alternative acceptable NMQSD therapeutic agent may be an NMOSD therapeutic agent that blocks a complement component, such as complement component C5, e.g., Eculizumab (also referred to as Soliris®; U.S. Patent 6,355,245). If the alternative acceptable NMOSD therapeutic agent is Eculizumab, then Eculizumab may be administered to the subject at a dose of approximately 900 mg once per rveek for four weeks, followed by a dose of approximately 1200 mg one week following the fourth 900 mg dose, further followed by a 900 mg dose every two weeks following the first 900 mg dose.
  • a complement component such as complement component C5
  • Eculizumab also referred to as Soliris®; U.S. Patent 6,355,245
  • Eculizumab may be administered to the subject at a dose of approximately 900 mg once per rveek for four weeks, followed by a dose of approximately 1200 mg one week following the fourth 900 mg dose, further followed by a 900 mg dose every
  • an alternative acceptable NMOSD therapeutic agent may be an NMOSD therapeutic agent that binds to and blocks interleukin (IL)-6 receptor (R). If the alternative acceptable NMOSD therapeutic agent hinds to and blocks IL-6R, the therapeutic agent may he Satralizumab (also referred to as SA-237; disclosed in U.S. Patent Application Publication 2018/0148509). If the therapeutic agent is Satralizumab, then Satralizumab may be administered to the subject subcutaneously at a dose of approximately 120 mg once every other week for an initial three doses, and then every fourth week after the administration of the initial three doses.
  • IL interleukin-6 receptor
  • NMOSD therapeutic agents may include azathioprine, prednisone, azathioprine in combination with prednisone, mycoph enolate, methotrexate, or methotrexate in combination with corticosteroids/cyclophosphamide, or others known in the art.
  • NMOSD-related damage is reduced in a subject who is at increased risk for NMOSD-reiated damage.
  • the subject may be identified as at increased risk for NMOSD-reiated damage if the subject comprises a sGFAP concentration of about 160 pg/mL, 160 pg/mL, about 165 pg/mL, 165 pg./mL, about 166 pg/mL, 166 pg/mL, about 167 pg/mL, 167, pg/mL, about 168 pg/mL, 168 pg/mL, about 169 pg/mL, 169 pg/mL, about 170 pg/mL, 170 pg/mL, about 171 pg/mL, 171 pg/mL, about 172 pg/mL, 172 pg/mL, about 173 pg/mL, 173 pg/mL, 173 p
  • the subject may be identified as at increased risk for NMOSD-reiated damage if the subject comprises a sGFAP concentration of between about 166 pg/mL and about 176 pg/mL, between about 167 pg/mL, and about 175 pg/mL, between about 168 pg/mL and about 174 pg/mL, or between about 169 pg/mL and about 173 pg/mL or greater.
  • the subject may be identified as at increased risk for NMOSD-reiated damage if the subject comprises an sGFAP concentration that is approximately 2 standard deviations above or 3 standard deviations above a healthy donor’s mean sGFAP concentration or greater.
  • the subject may comprise a sGFAP concentration of about, or approximately, 170 pg/'m L, e.g., a sGFAP concentration of 170 pg/mL, or greater.
  • a measurement of sGFAP concentration e.g., of 170 pg/mL
  • the subject also has an increase in serum Neurofilament light chain (Nfl) levels over baseline Nfl levels of the subject or as compared to a control subject.
  • the subject has a sGFAP concentration of about 160 pg/mL, 160 pg/mL, about 165 pg/mL, 165 pg/rnL, about 166 pg/rnL, 166 pg/mL, about 167 pg/mL, 167, pg/mL, about 168 pg/mL, 168 pg/mL, about 169 pg/mL, 169 pg/mL, about 170 pg/m L, 170 pg/mL, about 171 pg/m L, 171 pg/mL, about 172 pg/ ' niL, 172 pg/mL, about 173 pg/mL, 173 pg/mL, about 174
  • the NMOSD-related damage reduced by the methods may be: a reduction in number of NMOSD-related attacks in the at increased risk subject, a reduction in severity of NMOSD- related attacks in the at increased risk subject an improvement in recovers, ' from NMOSD- related attacks in the at increased risk subject, a reduction in number of magnetic resonance imaging (MRI) lesions in the at increased risk subject, a reduction in rate of increase in new MRI lesions in the at increased subject, a reduction in rate of worsening of Expanded Disability Status Scale (EDSS) score in the at increased risk subject, an improvement in EDSS score in the at increased risk subject, a reduction NMOSD-related pain in the at increased risk subject, or a reduction in NMOSD-related disability in the at increased risk subject.
  • MRI magnetic resonance imaging
  • EDSS Expanded Disability Status Scale
  • reducing the NMOSD-related damage in a subject in need thereof comprises: (a) reducing a number of magnetic resonance imaging (MRI) lesions, (b) reducing rate of increase in ne w MRI lesions; or (c) both (a) and (b).
  • the reducing the rate of increase can also refer to reducing appearance of new MRI lesions or reducing the rate of increase over a period of time.
  • the time can comprise a period of about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months.
  • the subject’s baseline number of NMOSD-related attacks may be the number of NMOSD-related attacks experienced by the subject during a first time period that precedes the administering of VIB551 or a derivative thereof.
  • the subject’s number of NMOSD-related attacks that are decreased, relative to baseline, may be the number of attacks experienced by the subject during a second time period following the administering of a first dose of a composition that comprises Inebilizumab or a derivative thereof.
  • the first and the second time period may or may not be of equal length.
  • the first and second time period may both be of a length in time of approximately 6 months, 6 months, approximately 12 months, 12 months, approximately 18 months, 18 months, approximately 24 months, 24 months, approximately 30 months, 30 months, approximately 36 months, 36 months, approximately 42 months, 42 months, approximately 48 months, 48 months, approximately 54 months, 54 months, approximately 60 months, 60 months, approximately 6 years, 6 years, approximately 7 years, 7 years, approximately 8 years, 8 years, approximately 9 years, 9 years, approximately 10 years, or 10 years. It will be understood that the first and the second time period need not be exactly the same length in time, i.e., need not be exactly the same number of days.
  • first and the second time period may be considered to be of equal length if the number of days of the first time period is greater or lesser than 10%, 8%, 6%, 4%, 2%, or 1% the number of days in the second time period.
  • the first time period which precedes the administering of a compositions that compri ses Inebilizumab or a derivative thereof and is the time period during which the baseline number of NMOSD-related attacks is determined, may end the day before the administering of Inebilizumab or the derivative thereof.
  • the first time period may end at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 10 days, at most 11 days, at most 12 days, at most 13 days, at most 14 days or at most 1 month before the administering of a compositions that comprises Inebilizumab or a derivative thereof.
  • the second time period which follows the administering of a composition that comprises Inebilizumab or a derivative thereof and is the time period during which the number of NMOSD-related attacks may be reduced, may begin the day of the administering of a first dose of Inebilizumab or derivative thereof.
  • the second time period may begin at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 10 days, at most 11 days, at most 12 days, at most 13 days or at most 14 days following the administering of the first dose of Inebilizumab or derivative thereof.
  • the number of NMOSD-related attacks in the subject at increased risk for NMOSD- related damage may be reduced during the second time period by at least 1, 1, at least 2, 2, at least 3, 3, at least 4, 4, at least 5, or 5 following the administering of Inebilizumab or the derivative thereof relative to baseline of the subject or as compared to a control subject,
  • the reduction in NMOSD-related damage may be a reduction in likelihood that the subject suffers a major NMOSD-related attack, e.g. attack graded major in severity. If the at increased risk subject is at a reduced likelihood of suffering a major NMOSD-related attack, then the reduced likelihood may he a prevention of the subject suffering the major NMOSD- related attack. Alternatively, the reduced likelihood may be a decrease in risk that the subject will suffer a major NMOSD-related attack of between 25% and 100%, or between 50% and 100%, or between 75% and 100% or between 25% and 75%, or between 50% and 75%, or by at least 25%, at least 50%, or at least 75%.
  • the reduction in likelihood that the at increased risk subject suffers a major NMOSD- related attack may be demonstrated by a reduction in number of severe NMOSD-related attacks experienced by the subject in a time period following the administering of a first dose of Inebilizumab or derivative thereof, (e.g., a second time period), relative to a time period preceding the administering of Inebilizumab or derivative thereof, (e.g., a first time period), in which the first and the second time period are of equal length.
  • the first and the second time period may be approximately 6 months, 6 months, approximately 12 months, 12 months, approximately 18 months, 18 months, approximately 24 months, 24 months, approximately 30 months, 30 months, approximately 36 months, 36 months, approximately 42 months, 42 months, approximately 48 months, 48 months, approximately 54 months, 54 months, approximately 60 months, 60 months, approximately 6 years, 6 years, approximately 7 years, 7 years, approximately 8 years, 8 years, approximately 9 years, 9 years, approximately 10 years, or 10 years. It will be understood that the first and the second time period need not be exactly the same length in time, need not be exactly the same number of days.
  • first and the second time period may be considered to be of equal length if the number of days of the first time period is greater or lesser than 10%, 8%, 6%, 4%, 2%, or 1% the number of days in the second time period.
  • the first time period, preceding the administering Inebilizumab or derivative thereof, may end the day before the administering of Inebilizumab or derivative thereof.
  • the first time period may end at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 10 days, at most 11 days, at most 12 days, at most 13 days, at most 14 days or at most 1 month before the administering of Inebilizumab or derivative thereof.
  • the second time period following the administering of a first dose of Inebilizumab or derivative thereof, and that is the time period over which the number of NMOSD-related attacks graded as severe may be reduced, may be a time period that begins the day of the administering of a first dose of Inebilizumab or derivative thereof.
  • the second time period may begin at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 1 0 days, at most 11 days, at most 12 days, at most 13 days or at most 14 days following the administering of the first dose of Inebilizumab or derivative thereof.
  • An NMOSD-related attack graded major in severity may be any NMOSD-related attack that, requires intensive therapeutic intervention, interrupts usual activities of daily living, significantly affects the subject’s clinical status, or requires in-subject hospitalization.
  • An NMOSD-related attack graded as major in severity may be an NMOSD- related attack that, if it affects brain, results in an increase in the subj ecr s brain domain subscale score of 2 or more points when compared to the subject’s brain domain subscale score prior to the NMOSD-related attack.
  • An NMOSD-related attack graded as major in severity may be an NMOSD-related attack that, if it affects any of the subject’s optic nerve, spinal cord or brainstem, results in the affected domain’s subscale score increasing by >3 points when compared the affected domain’s subscale score prior the attack, wherein the affected domain’s subscale score had been less than 2 prior to the NMOSD-related attack.
  • An NMOSD-related attack graded as major in severity may be an NMOSD-related attack that, if it affects any of the subject’s optic nerve, spinal cord or brainstem, results in the affected domain’s sub scale score increasing by >2 when compared the affected domain’s subscale score prior the attack, wherein the affected domain’s subscale score had been >2 prior to the NMOSD-related attack.
  • Domain subscale scores may be determined according to the domain numerical assignments presented in Table 2.
  • the NMOSD-related attacks may be attacks characterized by the appearance of a new NMOSD symptom or the worsening of an existing NMOSD symptom.
  • the new or worsening existing symptom which characterizes the NMOSD-related attack may be an eye symptom, a spinal cord symptom, a brain/brain stem symptom, or any combination thereof.
  • the NMOSD-related attack if characterized by a new or worsening eye symptom may be characterized by eye pain, a new optic nerve lesion, an enlarging optic nerve lesion, blurred vision, loss of vision, or a 5 or more character drop in low-contrast Landolt C Broken Rings Chart.
  • the NMOSD-related attack if characterized by a new or worsening eye symptom, may further/ alternatively meet any one or more of the following criteria: > 15-character drop in high-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in a previously affected eye and no other ophthaimological explanation; reduction of >2 steps in counting fingers (CF) to no light perception (NLP) from most recent clinical visit as measured in a previously affected eye and no other ophthaimological explanation; reduction of >7 characters in low-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and a new relative afferent pupillary defect (RAPD) in affected eye; reduction of >7 characters in low-contrast Landolt C Broken Ring Chart, from most recent clinical visit as measured in either eye alone (monocular) and loss of a previously documented RAPD in fellow eye; reduction of >5 characters in high-contrast Landolt C Broken Ring Chart from most recent clinical visit
  • the NMOSD-reiated attack if characterized by a new or worsening spinal cord symptom, may be characterized by deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • the NMOSD-reiated attack if characterized by a new or worsening spinal cord symptom, may further/alternatively meet any one or more of the following criteria: Worsening of >2 points in at least one of the relevant (pyramidal, bladder/bowel, sensory) Functional Systems Scores (FSS) compared with most recent clinical visit; worsening of >1 point in EDSS score compared with most recent clinical visit if previous EDSS score >5-5; worsening of >1 point in at least two of the relevant (pyramidal, bladder/bowel, sensory) FSS compared with most recent clinical visit when the most recent clinical visit score was >1 and a new 7 Gd- enhancing or new/ enlarging T2 MRI lesion in the spinal cord; worsening of >0 .5 points in EDSS score compared with most recent visit if previous EDSS score >5-5 and a new Gd- enhancing or new/enlarging T2 MRI lesion in the spinal cord.
  • FSS Functional Systems
  • the NMOSD-reiated attack if characterized by a brain or brain stem symptom, may be characterized by nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • the NMOSD-related attack if characterized by a new or worsening existing symptom, may further/alternatively meet any one or more of the following criteria: isolated (not present at most recent clinical visit) intractable nausea, vomiting, and/or hiccups lasting >48 hours and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; worsening of >2 points in at least one of the relevant (brainstem, cerebellar) FS8 compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; or worsening of >2 points in at least one of the relevant (cerebral, sensory, pyramidal) FSS (with a score of >3 at the current visit) compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation.
  • the reduction in NMOSD-related damage may be a reduction in number of MRI lesions or a reduction in rate of increase in new MRI lesions in the at increased risk subject. If the reduction in NMOSD-related damage comprises a reduction in number of MRI lesions, the number of MRI lesions may be reduced by at least 1 lesion, at least 2 lesions, at least 3 lesions, at least 4 lesions, at least 5 lesions, at least 6 lesions, at least 7 lesions, at least 8 lesions, at least
  • the reduction in number of MRI lesions may occur within approximately 2 months, approximately 4 months, approximately 6 months, approximately 8 months, approximately 10 months, approximately 12 months, approximately 18 months or approximately 24 months following the administering of a first dose of Inebilizumab or derivative thereof.
  • the reduction in number of MRI lesions may occur within 2 to 12 months, within 4 to 12 months, within 6 to 12 months, within 8 to 12 months, or within
  • rate in increase may be reduced by approximately 10%, 10%, approximately 20%, 20%, approximately 30%, 30%, approximately 40%, 40%, approximately 50%, 50%, approximately 60%, 60%, approximately 70%, 70%, approximately 80%, 80%, approximately 90%, 90% or approximately 100% relative to rate of increase in new MRI lesions prior to the administering of a first dose of Inebilizumab or derivative thereof.
  • the reduction in rate of increase in number of MRI lesions may be a reduction in rate of increase of between 25% and 100%, between 50% and 100%, between 75% and 100%, between 25% and 75%, or between 50% and 75% relative to rate of increase in new MRI lesions prior to the administering of a first dose of Inebilizumab or derivative thereof.
  • the reduction in rate in increase in new MRI lesions may be determined by comparing the rate of increase in new MRI lesions in the subject within a first time period, prior to the administering of Inebilizumab or derivative thereof, to the rate of increase in MRI lesions in the subject in a second time period, following the administering of a first dose of Inebilizumab or derivative thereof to the subject.
  • the first and the second time period may be of an equal length in time and may be of a length in time of approximately 6 months, 6 months, approximately 12 months, 12 months, approximately 18 months, 18 months, approximately 24 months, 24 months, approximately 30 months, 30 months, approximately 36 months, 36 months, approximately 42 months, 42 months, approximately 48 months, 48 months, approximately 54 months, 54 months, approximately 60 months, 60 months, approximately 6 years, 6 years, approximately 7 years, 7 years, approximately 8 years, 8 years, approximately 9 years, 9 years, approximately 10 years, or 10 years. It will be understood that the first and the second time period need not be exactly the same length in time, i.e., need not be exactly the same number of days.
  • the first and the second time period may be considered to be of equal length if the number of days of the first time period is greater or lesser than 10%, 8%, 6%, 4%, 2%, or 1% the number of days in the second time period.
  • the first time period may end at most 1 day, at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 10 days, at most 11 days, at most 12 days, at most 13 days, at most 14 days or at most 1 month before the administering of Inebilizumab or the derivative thereof.
  • the second time period may begin the day of the administering of a first dose of Inebilizumab or the derivative thereof.
  • the second time period may begin at most 2 days, at most 3 days, at most 4 days, at most 5 days, at most 6 days, at most 7 days, at most 8 days, at most 9 days, at most 10 days, at most 11 days, at most 12 days, at most 13 days, at most 14 days following the administering of a first dose of Inebilizumab or derivative thereof.
  • the MRI lesions may be brain lesions, brainstem lesions, spinal cord lesions, optic nerve lesions, or any combination of any two or more of brain, brainstem, spinal cord, and optic nerve lesions.
  • the MRI lesions may be clinically symptomatic lesions or clinically asymptomatic lesions.
  • the MRI lesions may be detected as T2 lesions and/or may be detected using gadolinium as a contrast medium and/or may be detected as gadolinium T1 lesions.
  • the reduction in NMOSD-related damage may comprise an improvement in EDSS score or a reduction in rate of worsening in EDSS score in the at increased risk subject. If the reduction in NMOSD-related damage comprises an improvement in the subject’s EDSS score, then the improvement may be a decrease in the subject’s EDSS score of at least .5 points, or at least 1 point, or at least 1.5 points, or at least 2 points following the administering of Inebilizurnab or derivative thereof.
  • the decrease in the subject’s EDSS score may occur within 2 weeks, 1 month, 1.5 months, 2 months, 2.5 months, or 3 months following the administering of a first dose of Inebilizumab or derivative thereof
  • the decrease in the subject’s EDSS score of the at least .5, at least 1, at least 1.5, or at least 2 points may be a decrease that, once initiated, may continue for a period of time of approximately 1 month, 1 month, approximately 2 months, 2 months, approximately 3 months, 3 months, approximately 4 months, 4 months, approximately 5 months, 5 months, approximately 6 months, 6 months, approximately 9 months, 9 months, approximately 12 months, 12 months, approximately 18 months, 18 months, approximately 24 months, or 24 months.
  • any continued decrease in EDSS score is a reference to the subject’s EDSS score being decreased relative to the subject’s EDSS score prior to the administering of a first dose of Inebilizumab or derivative thereof, e.g., no requirement that the subject’s EDSS score be decreased to be at the same number or to the same degree throughout the entire continued period of time.
  • the reduction in NMOSD-related damage comprises a reduction in rate of worsening in EDSS score
  • the reduction in rate of worsening in EDSS score in the at increased risk subject may be, if the subject has a baseline EDSS score of 0, a worsening to at most an EDSS score of .5, an EDSS score of at most 1, an EDSS score of at most 1.5, or an EDSS score of at most 2 over a period of time of at least 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years.
  • the reduction in rate of worsening in EDSS score in the at increased risk subject may be, if the subject has a baseline EDSS score of 1 to 5, a worsening of the subject’s EDSS score by .5 points or by no more than 1 point over a period of time.
  • the period of time in which the subject with the baseline score of 1 to 5 worsens by the .5 points, or by the no more than 1 point may be a period of time of at least 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years .
  • the reducti on in rate of worsening in EDSS score in the at increased risk subject following administering Inebilizumab or the derivative thereof may be, if the subject has a baseline EDSS score of 5.5 or more, a worsening of the subject’s EDSS score by no more than .5 points over a period of time.
  • the period of time in which the subject with the baseline score of 5.5 worsens by the no more than .5 points may be a period of time of at least. 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years.
  • the subject’s baseline EDSS score may be determined approximately 1 month, 2 weeks, 1 week, 3 days, 2 days, or 1 day prior to the administering of a first dose of Inebilizumab or derivative thereof.
  • NMOSD relapse is prevented in a subject diagnosed with NMOSD.
  • the present disclosure also provides methods of reducing the likelihood of NMOSD relapse in a subject diagnosed with NMOSD.
  • the subject may be identified as a subject for preventing NMOSD relapse or reducing the likelihood of NMOSD relapse if the subject compri ses a sGFAP concentration of less than about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, about 173 pg/mL, about 174 pg/mL, about 175 pg/mL, about 176 pg/mL, or about 181 pg/mL.
  • a subject may be identified as a subject for preventing NMOSD relapse or reducing the likelihood of NMOSD relapse if the subject comprises a sGFAP concentration of about 165 pg/mL, 165 pg/mL, about 166 pg/mL, 166 pg/mL, about 167 pg/mL, 167 pg/mL, about 168 pg/mL, 168 pg/mL, about 169 pg/mL, 169 pg/mL, about 170 pg/mL, 170 pg/mL, about 171 pg/mL, 171 pg/mL, about 172 pg/mL, 172 pg/mL, about 173 pg/mL, 173 pg/mL, about 174 pg/mL, 174 pg/mL, about 175 pg/mL, 175 pg/mL, 175
  • the subject may be identified as a subject for preventing or reducing the likelihood of NMOSD relapse if the subject comprises a sGFAP concentration of between about 165 pg/mL and about 181 pg/mL, between about 167 pg/mL and about 175 pg/mL, between about 168 pg/mL and about 174 pg/mL, or between about 169 pg/mL and about 173 pg/mL or less. Further, the subject may be identified as a subject for preventing or reducing the likelihood of NMOSD relapse if the subject comprises an sGFAP concentration that is less than approximately 2 standard deviations above or 3 standard deviations above a healthy donor’s mean sGFAP concentration.
  • the subject may be identified as a subject for preventing or reducing the likelihood of NMOSD relapse if the subject comprises a sGFAP concentration that is approximately, or about, 170 pg/mL, e.g., 170 pg/mL, or less.
  • a sGFAP concentration that is approximately, or about, 170 pg/mL, e.g., 170 pg/mL, or less.
  • an approximate sGFAP concentration e.g., of 170 pg/mL
  • an sGFAP concentration may be an sGFAP concentration that takes into account any deviation or variation, e.g., from 170 pg/mL, caused by a device employed to measure sGFAP concentration, e.g., device calibration, or sample handling or processing leading up to measurement of sGFAP concentration.
  • 176 pg/mL, 176 pg/mL, about 181 pg/mL, or 181 pg/mL or less may further not have experienced an NMOSD-related attack in at least 2 months, at least 3 months, at least 4 months, at least 5 months, or at least 6 months.
  • a subject with NMOSD is identified as a subject for treatment with Inebilizumab if the subject has an increase in serum Neurofilament light chain (Nil) levels over baseline levels of the subject or as compared to a control subject.
  • a subject identified as at increased risk for NMOSD-related disability if the subject has an increase in serum NfL levels over baseline levels or as compared to a control subject.
  • a composition that, comprises Inebilizumab or a derivative thereof is administered to a subject diagnosed with NMOSD with an increase in serum Nfl levels over baseline levels or as compared to a control subject.
  • subjects diagnosed with NMOSD with an increase in serum Nfl levels are treated with Inebilizumab or a derivative regardless of if they have had an attack.
  • methods of treating NMOSD in a subject comprising administering a composition that comprises Inebilizumab to a subject with an increase in serum Nfl levels over a baseline level of the subject or as compared to a control subject.
  • the disclosure provides methods of treating NMOSD in a subject, the methods comprising a therapy or administering a therapeutic to a subject with an increase in serum Nfl levels over a baseline level or as compared to a control subject.
  • the therapy or therapeutic comprises administering one or more of Eculizumab, Satralizumab, Ublituximab, Kavulizumab, Rituximab, azathioprine, mycophenolate mofetil or low dose corticosteroids.
  • a therapeutic is selected from the group consisting of. Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, azathioprine, mycophenolate mofetil, and low dose corticosteroid.
  • baseline levels of serum Nfl refer to the level of serum Nfl measured at a time before an NMOSD-related attack.
  • the subject has an about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0 or greater fold change over baseline levels.
  • subjects with an increase in serum Nfl levels over baseline levels are treated with a composition that comprises Inebilizumab or a derivative thereof as descried in any method disclosed herein.
  • An NMOSD-related attack which may further not have been experienced by the subject, may be an attack characterized by the appearance of a new NMOSD symptom or the worsening of an existing NMOSD symptom. If such an NMOSD-related attack is characterized by a new or worsening existing NMOSD symptom, the symptom may be an eye symptom, a spinal cord symptom, a brain/brain stem symptom, or any combination thereof.
  • the new or worsening eye symptom may be eye pain, a new optic nerve lesion, an enlarging optic nerve lesion, blurred vision, loss of vision, or a 5 or more character drop in low-contrast Landolt C Broken Rings Chart.
  • the subject may not have experienced a new or worsening existing eye symptom that further/altematively meeting any one or more of the following criteria: > 15-character drop in high-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in a previously affected eye and no other ophthalmological explanation; reduction of >2 steps in CF to NLP from most recent clinical visit as measured in a previously affected eye and no other ophthaimological explanation; reduction of >7 characters in low-contrast Landoit C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and a new relative afferent pupillary defect (RAPD) in affected eye; reduction of >7 characters in low-contrast Landoit C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and loss of a previously documented RAPD in fellow eye; reduction of >5 characters in high-contrast Landoit C Broken Ring Chart from most recent clinical visit as measured
  • the subject may not have experienced a new or worsening spinal cord symptom, such as a deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • a new or worsening spinal cord symptom such as a deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • the subject may not have experienced a new or worsening existing spinal cord symptom that further/alternatively meets any one or more of the following criteria: Worsening of >2 points in at least one of the relevant (pyramidal, bladder/bowel, sensory) FSS compared with most recent clinical visit; worsening of >1 point in EDSS score compared with most recent clinical visit if previous EDSS score >5-5; worsening of >1 point in at least two of the relevant (pyramidal, bladder/bowel, sensory) FSS compared with most recent clinical visit when the most recent clinical visit score was >1 and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord; worsening of >0-5 points in EDSS score compared with most recent visit if previous EDSS score >5-5 and a new GD-enhancing or new/enlarging T2 MRI lesion in the spinal cord
  • the subject may not have experienced a new or worsening brain or brain stem symptom such as nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • a new or worsening brain or brain stem symptom such as nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • the subject may not have experienced a new or worsening existing brain or brain stem symptom that further/alternatively meets any one or more of the following criteria: isolated (not present at most recent clinical visit) intractable nausea, vomiting, and/or hiccups lasting >48 hours and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; worsening of >2 points in at least one of the relevant (brainstem, cerebellar) FSS compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; or worsening of >2 points in at least one of the relevant (cerebral, sensory, pyramidal) FSS (with a score of >3 at the current visit) compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation.
  • the subject may be administered a composition that comprises Inebilizumab or a derivative thereof.
  • the administration of Inebilizumab or the derivative thereof may be intravenously at a dose of 300 mg every six months.
  • the administering of Inebilizumab or a derivative thereof to the subject results in the preventing NMQSD relapse or reducing the likelihood of NMQSD relapse in the subject.
  • the preventing NMQSD relapse or reducing the likelihood of NMQSD relapse in the subject may be a prevention of NMOSD-related attacks in the subject.
  • the preventing NMQSD relapse or reducing the likelihood of NMQSD relapse in the subject may, alternatively, prevent the worsening of any one or more NMOSD-related symptoms in the subject, even if the one or more NMSOD-related symptoms are not associated with an NMOSD-related attack.
  • the NMO SD -related symptoms may be clinical or may be subclinical symptoms.
  • the NMOSD-related symptoms may comprise one or more eye symptoms, spinal cord symptoms, brain symptoms or brain step symptoms. If the one or more NMOSD-related symptoms comprise an eye symptom, the eye symptom may be eye pain, a new optic nerve lesion, an enlarging optic nerve lesion, blurred vision, loss of vision, or a 5 or more character drop in low- contrast Landolt C Broken Rings Chart.
  • the NMOSD-related symptoms may be deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • the one or more NMQSD-reiaied symptoms comprise a brain or brain stem symptom
  • the NMOSD-related symptoms may be nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • the NMOSD-related symptoms may include any other symptom or criteria described as characterizing an NMQSD-reiaied atack, the absence of wTsich identified a subject as a subject for preventing relapse.
  • the preventing NMQSD relapse or reducing the likelihood of NMQSD relapse in the subject may result in a reduction in MRI lesions in the subject.
  • the reduction in MRI lesions may refer to a reduction in the number of MRI lesions in the sub j ect, a reduction in the number of enlarging MRI lesions in the subject, or a reduction in the combined number of MRI lesions and enlarging MRI lesions in the subject.
  • the reduction in MRI lesions in the subject may be a reduction of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 lesions.
  • the reduction in MRI lesions in the subject may occur within approximately 2 months, approximately 4 months, approximately 6 months, approximately 8 months, approximately 10 months, approximately 12 months, approximately 18 months or approximately 24 months of the administering of a first dose of Inebilizumab or derivative thereof.
  • the reduction in number of MRI lesions may occur within 2 to 12 months, within 4 to 12 months, within 6 to 12 months, within 8 to 12 months, or within 10 to 12 months of the administering of a first dose of Inebilizumab or derivative thereof
  • the MRI lesions may be lesions in any one or more of the optic nerve, spinal cord, brain or brain stem of the subject.
  • the MRI lesions may be asymptomatic MRI lesions.
  • a composition that comprises Inebilizumab or a derivative is admini stered to a subj ect who i s suspected of having NMG SD .
  • the NMOSD-related symptoms may be clinical or may be subclinical symptoms.
  • the NMOSD-related symptoms may comprise one or more eye symptoms, spinal cord symptoms, brain symptoms or brain step symptoms.
  • the eye symptom may be eye pain, a new optic nerve lesion, an enlarging optic nerve lesion, blurred vision, loss of vision, or a 5 or more character drop in low-contrast Landolt C Broken Rings Chart.
  • the one or more NMOSD-related symptoms comprise a spinal cord symptom
  • the NMOSD-related symptoms may he deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • the NMOSD-related symptoms comprise a brain or brain stem symptom
  • the NMOSD-related symptoms may be nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • the NMOSD-related symptoms may include any other symptom or criteria described as characterizing an NMOSD-related attack, the absence of which identified a subject as a subject for preventing relapse.
  • a composition that comprise Inebilizumab is administered to a subject suspected of having NMOSD with an increase in serum Nil levels over baseline levels.
  • a therapy is administered to a subject suspected of having NMOSD with an increase in serum Nil levels over baseline levels or as compared to a control subject.
  • the therapeutic comprises one or more of Eculizumah, Satralizumab, Ublituximab, Ravulizumab, Rituximab, azathioprine, mycophenolate mofetil or low dose corticosteroids.
  • EDSS score 1 point, or at least 1.5 points, or at least 2 points following the administering of a first dose of Inebilizumab or derivative thereof.
  • the decrease in the subject’s EDSS score may begin within
  • the decrease in the subject’s EDSS score of the at least .5, at least 1, at least 1 .5, or at least 2 points may be a decrease that, once initiated, may continue for a period of time of approximately 1 month, 1 month, approximately 2 months,
  • any continued decrease in EDSS score is a reference to the subject’s EDSS score being decreased relative to the subject’s EDSS score prior to administering of a first dose of Inebilizumab or derivative thereof, e.g., no requirement that the subject’s EDSS score be decreased to be at the same number or to the same degree throughout the entire continued period of time,
  • the preventing NMOSD relapse or reducing the likelihood of NMOSD relapse in the subject identified as a subject for preventing or reducing the likelihood of NMOSD relapse may be for a time period of at least 1 year from the administering of a first dose of Inebilizumab or derivative thereof.
  • preventing or reducing the likelihood of NMOSD relapse in the subject identified as a subject for preventing or reducing the likelihood of NMOSD relapse may be for a time period of at least 1.5 year, at least 2 years, at least 2.5 years, at least
  • the subject’s sGFAP concentration may decrease. If the subject’s sGFAP concentration decreases, the decrease may be a decrease of 2% to 30%, 5% to 25%, 5% to 20%, 10% to 20%, 10% to 30%, or 5% to 30%. Alternatively, the subject’s sGFAP concentration may decrease by approximately 2%, 2%, approximately 5%, 5%, approximately 10%, 10%, approximately 15%, 15%, approximately 20%, 20%, approximately 25%, 25%, approximately 30%, or 30%.
  • the subject’s decrease in sGFAP concentration may be a decrease that, once initiated, may continue for a period of time of approximately 1 month, 1 month, approximately 2 months, 2 months, approximately 3 months, 3 months, approximately 4 months, 4 months, approximately 5 months, 5 months, approximately 6 months, 6 months, approximately 9 months, 9 months, approximately 12 months, 12 months, approximately 18 months, 18 months, approximately 24 months, or 24 months.
  • any continued decrease in sGFAP concentration is a reference to the subj ecf s sGFAP concentration being decreased relative to the subj ecf s sGFAP concentration prior to administering of a first dose of Inebilizumab or derivative thereof, i.e., there is no requirement that the subject’s sGFAP concentration be decreased at the same number or to further decrease throughout the entire continued period of time.
  • the subject is identified as being at risk for an NMOSD-related attack, e.g:, is identified as an at-risk subject, if the subject comprises an increase in sGFAP concentration relative to his or her baseline sGFAP concentration or as compared to a control subject.
  • the subject’s baseline sGFAP concentration, against which an increase in sGFAP concentration identifies the subject as at-risk may be the subject’s sGFAP concentration at any time he or she is not experiencing an NMOSD-related attack and not within one week, or two weeks, or three weeks of experiencing an NMOSD-related attack.
  • the increase in sGFAP concentration relative to baseline sGFAP concentration may differ depending on wh ether the subject is undergoing a treatment for NMOSD that comprises Inebilizumab or a derivative thereof.
  • the subject may be identified as at-risk for an NMOSD-related attack if the subject’s sGFAP concentration increases at least 25-fold, 25-fold, at least 20-fold, 20-fold, at least 15-fold, 15-fold, at least 10-fold, 10-fold, at least 5-fold, 5-fold, at least 2-fold, 2-fold, between 25-fold and 5-fold, between 20-fold and 5-fold, between 15-fold and 5-fold, between 10-fold and 5-fold, between 25-fold and 10-fold, between 25-fold and 15-fold, or between 25- fold and 20-fold relative to baseline or as compared to a control subject.
  • the increase in sGFAP concertation occurs or is detected over a period of about: 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months,
  • treatment for NMOSD does not comprise Inebilizumab or a derivative thereof, then the subject may not be undergoing any treatment for NMOSD, or the subject may be undergoing treatment for NMOSD with any non- Inebilizumab or non- Inebilizumab derivative treatment known in the art to have been used for the treatment of NMOSD, e.g., azathioprine, mycophenolate mofetil or low dose corticosteroids.
  • the subject may be identified as at-risk for an NMOSD- related attack if the subject’s sGFAP concentration, relative to baseline, increases by at least 25%, 25%, at least 50%, 50%, at least 75%, 75%, at least 100%, 100%, at least 125%, 125%, at least 150%, 150%, at least 175%, 175%, at least 200%, 200%, between 25% and 200%, between 50% and 200%, between 75% and 200%, between 100% and 200%, between 125% and 200%, between 150% and 200%, between 175% and 200%, between 25% and 50%o, between 25% and 75%, between 25% and 100%, between 25% and 125%, between 25% and 150%, between 25% and 175%, between 50% and 150%, between 75% and 125%, between 100% and 200%, or between 50% and 100%.
  • a therapeutic may be administered to the at-risk subject.
  • Administration of the therapeutic to the at-risk subject may occur at most one week following the subject’s identification as an at-risk subject.
  • administration of the therapeutic to the at-risk subject may occur at most 6 days, at most 5 days, at most 4 days, at most 3 days, at most 2 days or at most 1 day following the subject’s identification as an at-risk subject.
  • a therapeutic is administered to an at-risk subject at. most about one rveek, at most 6 days, at most 5 days, at most 4 days, at most 3 days, at most 2 days or at most 1 day following the subject’s identification as at-risk.
  • a therapeutic may comprise one or more of a high dose steroid, plasmapheresis, immunoad sorption, a complement inhibitor, or any other agent not included as part of the at-risk subject’s treatment regimen at the time the subject is identified as being at-risk.
  • a therapeutic is selected from the group consisting of. a high dose steroid, plasmapheresis, immunoadsorption, and a complement inhibitor.
  • a therapy is administered to an at-risk subject within at most one week, at most 6 days, at most 5 days, at most 4 days, at most 3 days, at most 2 days or at most 1 day following the subject’s identification as at-risk.
  • a therapeutic may comprise or may further comprise a composition comprising Inebilizumab or a derivative thereof, if the at-risk subject’s treatment regimen at the time of identification, did not comprise a composition comprising Inebilizumab or a derivative thereof.
  • Inebilizumab or the derivative thereof may be administered to the at-risk subject at a dose of approximately 300 mg.
  • An approximately 300 mg dose may be a dose of about 250 mg to about 350 mg, it may be a dose of about 275 mg to about 325 mg, it may be a dose of about 290 mg to about 310 mg, it may be a dose of about 205 mg to about 305 mg, or it may be a dose of 275 mg, 280 mg, 285 mg, 290 mg, 295 mg, 300 mg, 305 mg, 310 mg, 315 mg, 320 mg, or 325 mg,
  • the therapy administered to the at-risk subject is Inebilizumab or a derivative thereof
  • the subject may continue therapy with Inebilizumab or the derivative thereof following the administering of a first dose of Inebilizumab or the derivative thereof.
  • a second Inebilizumab or derivative thereof dose may be administered to the at-risk subject approximately two weeks after the first dose, and third and subsequent doses may be administered to the at-risk subject at a time interval of approximately 6 months following their preceding dose.
  • the third and subsequent Inebilizumab or derivative thereof doses may be administered to the subject identified as at-risk at a time interval of approximately 180 days, between 170 and 190 days, between 175 and 185 days, between 175 and 190 days, between 170 and 185 days, approximately 26 weeks, approximately 25 weeks, approximately 27 weeks, between 25 and 27 weeks, between 25 and 26 weeks, or between 26 and 27 weeks following their preceding dose.
  • the suppressing the NMOSD-related attack in the at-risk subject may reduce the likelihood of or prevent the MvIOSD-related attack in the at-risk subject. If the suppressing the NMOSD-related attack reduces the likelihood of the NMOSD-related in the at-risk subject then the reduced likelihood may decrease the risk of the at-risk subject suffering an NM OSD- related attack by approximately 10%, 10%, approximately 20%, 20%, approximately 30%, 30%, approximately 40%, 40%, approximately 50%, 50%, approximately 60%, 60%, approximately 70% 70%, approximately 80%, 80%, approximately 90%, or 90%, The suppressing the NMOSD-related attack in the at-risk subject may, alternatively, prevent the subject from experiencing an NMOSD-related attack or symptoms of an NMOSD-related attack.
  • the suppressing the NMOSD-related attack in the at-risk subject may result in a reduction in likelihood or prevention of the at-risk subject suffering any NMOSD-related attack graded major in severity.
  • An NMOSD-related attack graded major in severity may be an NMOSD-related attack that resultantly requires intensive therapeutic intervention, interrupts usual activities of daily living, significantly affects the subject’s clinical status, or requires insubject hospitalization.
  • An NMOSD -related attack graded as major in severity may be an NMOSD-related attack that, if it affects brain, results in an increase in the subject’s brain domain subscale score of 2 or more points when compared to the subject’s brain domain subscale score prior to the NMOSD-related attack.
  • An NMOSD-related attack graded as major in severity may be an NMOSD-related attack that, if it affects any of the subject’s optic nerve, spinal cord or brainstem, results in the affected domain’s subscale score increasing by >3 points when compared the affected domain’s subscale score prior the attack, wherein the affected domain’ s subscale score had been less than 2 prior to the NMOSD-related attack.
  • NMOSD-related attack graded as major in severity may be an NMOSD-related attack that, if it affects any of the subject’s optic nerve, spinal cord or brainstem, results in the affected domain’s sub scale score increasing by >2 when compared the affected domain’s subscale score prior the attack, wherein the affected domain’s subscale score had been >2 prior to the NMOSD-related attack.
  • Domain subscale scores may be determined according to the domain numerical assignments presented in Table 2,
  • the suppressing the NMOSD-related attack in the at-risk subject may result in a recovery from the NMOSD-related attack that is graded as major.
  • a recovery from an NMOSD-related attack that affects brain may be graded as maj or if the recovery from the attack comprises an improvement in the subject’s brain subscale score of greater than 1 in a follow- up to the attack.
  • a recovery from an NMOSD-related attack that affects a subject’s optic nerve, spinal cord or brainstem may be graded as major if the recovery from the attack improves the subject’s affected (optic nerve, spinal cord or brainstem) domain subscale score by >2 in a follow-up to the attack.
  • the follow' up to the attack, at which time a subject’s subscaie score in the affected domain is assessed for determining the grading of the recovery', may take place approximately 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, or 16 weeks after the NMOSD-related attack.
  • Domain subscaie scores may be determined according to the domain numerical assignments presented in Table 2.
  • the NMOSD-related attacks may be attacks characterized by the appearance of a new NMOSD symptom or the worsening of an existing NMOSD symptom.
  • the new' or worsening existing symptom which characterizes the NMOSD-related attack may be an eye symptom, a spinal cord symptom, a brain/brain stem symptom, or any combination thereof.
  • the eye symptom may be eye pain, a new optic nerve lesion, an enlarging optic nerve lesion, blurred vision, loss of vision, or a 5 or more character drop in low-contrast Landolt C Broken Rings Chart.
  • the NMQSD-related attack may further/alternatively meet any one or more of the following criteria: >15-character drop in high-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in a previously affected eye and no other ophthalmological explanation; reduction of >2 steps in CF to NLP from most recent clinical visit as measured in a previously affected eye and no other Ophthalmol ogical explanation, reduction of >7 characters in low-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and a new RAPD in affected eye; reduction of >7 characters in low-contrast landolt C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and loss of a previously documented RAPD in fellow eye; reduction of >5 characters in high-contrast Landolt C Broken Ring Chart from most recent clinical visit as measured in either eye alone (monocular) and a new
  • the spinal cord symptom may be a deep or radicular pain, extremity paresthesia, weakness, sphincter dysfunction, Lhermitte’s sign, a new spinal cord lesion, or an enlarging spinal cord lesion.
  • the NMOSD-related attack is characterized by a new or worsening spinal cord symptom, it may further/altematively meet any one or more of the following criteria: Worsening of >2 points in at least one of the relevant (pyramidal, bladder/bowel, sensory) FSS compared with most recent clinical visit; worsening of >1 point in EDSS score compared with most recent clinical visit, if previous EDSS score >5-5; worsening of >1 point in at least, two of the relevant (pyramidal, bladder/bowel, sensory) F8S compared with most recent clinical visit when the most recent clinical visit score was >1 and a new Gd-enhancing or new/enlarging T2 MRI lesion in the spinal cord, worsening of >0-5 points in EDSS score compared with most recent visit if previous EDSS score >5 -5 and a new GD-enhancing or new/enlarging T2 MRI lesion in the spinal cord.
  • the brain or brain stern symptom may be nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, a new brain or brain stem lesion, or an enlarging brain or brain stem lesion.
  • the NMOSD-reiated attack is characterized by a new or worsening brain/brain stem symptom, it may further/alternatively meet any one or more of the following criteria: isolated (not present at most recent, clinical visit) intractable nausea, vomiting, and/or hiccups lasting >48 hours and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; worsening of >2 points in at least, one of the relevant (brainstem, cerebellar) FSS compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brainstem; or worsening of >2 points in at least one of the relevant (cerebral, sensory, pyramidal) FSS (with a score of >3 at the current visit) compared with most recent clinical visit and a new Gd-enhancing or new/enlarging T2 MRI lesion in the brain consistent with the clinical presentation.
  • the administration of the therapeutic to the subject identified as at-risk may result in a prevention of new MRI lesions in the at-risk subject.
  • the MRI lesions may be clinically symptomatic or clinically asymptomatic lesions.
  • the MRI lesions may be brain lesions, brainstem lesions, spinal cord lesions, optic nerve lesions, or any combination of any two or more of brain, brainstem, spinal cord, and optic nerve lesions.
  • the MRI lesions may be lesions detected as T2 lesions and/or using gadolinium as a contrast medium.
  • the administration of the therapeutic to the subject identified as at-risk may result in a reduction in NMOSD-reiated disability in the at-risk subject.
  • a reduction in NMOSD-reiated disability may be a reduction in worsening of NMOSD-reiated disability, or it may be a decrease in NMOSD-reiated disability, in the at-risk subject.
  • the NMOSD-reiated disability reduced in the at-risk subject may be a neurological disability or a manifestation of a neurological disability.
  • the NMOSD- reiated disability reduced in the at-risk subject may be one characterized by one or more of eye pain, a loss of color vision, an overall loss of vision, blurred vision, double vision, overall weakness or paralysis, weakness or paralysis in the arms or legs, radicular pain, uncontrollable hiccups, uncontrollable nausea or vomiting, loss of bladder or bowel control, paralysis, and/or fatigue.
  • a reduction in worsening in disability in the at-risk subject may be a reduction in worsening of the at-risk subject’s EDSS score.
  • a reduction in worsening of the at-risk subject’s EDS8 score if the at-risk subject has a baseline EDSS score of 0, may be a worsening of the at-risk subject’s EDSS score to a score of .5, or to a score of no more than 1, or to a score of no more than 1.5, or to a score of no more than 2 over a period of time.
  • the period of time in which the at-risk subject with the baseline score of 0 worsens to a score of .5, to no more than 1, to no more than 1.5, or to no more than 2 may be at least 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years.
  • a reduction in the worsening of the at-risk subject’s EDSS score, if the at-risk subject has a baseline EDSS score of 1 to 5, may be a reduction in worsening of the at-risk subject’s EDSS score by .5 points or by no more than 1 point over a period of time.
  • the period of time over which the at-risk subject with the baseline score of 1 to 5 worsens by .5 points, or by no more than 1 point may be at least 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years. If the reducing the NM OSD-related disability is a reduction in the worsening in the at-risk subject’s EDSS score, and the at-risk subject has a baseline EDSS score of 5.5 or more, then the reduction in worsening may be a worsening of the at-risk subject’s EDSS score by no more than .5 points.
  • the period of time in which the at-risk subject with the baseline score of 5.5 worsens by the no more than .5 points may be at least 6 months, 9 months, 1 year, 1.5 years, 2 years, 3 years, 4 years, 5 years, 7.5 years, or 10 years.
  • the at-risk subject’s baseline EDSS score may be determined approximately 1 month, 2 weeks, 1 week, 3 days, 2 days, or 1 day- prior to the administering of a first dose of Inebilizumab or derivative thereof.
  • a therapeutically effective amount of B cell depleting therapy may be administered to the subject when the subject has a sGFAP concentration of about 160 pg/mL, 160 pg/mL, about 165 pg/mL, 165 pg/mL, about 166 pg/mL, 166 pg/mL, about 167 pg/mL, 167 pg/mL, about 168 pg/mL, about 169 pg/mL, 169 pg/mL, about 170 pg/mL, 170 pg/mL, about 171 pg/mL, 171 pg/mL, about 172 pg/mL, 172 pg/mL, about 173 pg/mL, 173 pg/mL or greater.
  • the therapeutically effective amount of the B cell depleting therapy may be administered to the subject wh en the subject has a sGFAP concentration of between about 160 pg/mL and about 176 pg/mL, between about 167 pg/mL and about 175 pg/mL, between about 168 pg/mL and about 174 pg/mL, or between about 169 pg/mL and about 173 pg/mL or greater.
  • the therapeutically effect amount of the B cell depleting therapy may be administered to the subject when the subject has a sGFAP concentration that is approximately 2 standard deviations above or 3 standard deviations above a healthy donor’s mean sGFAP concentration or greater.
  • the subject may have a sGFAP concentration of approximately, or about, 170 pg/mL, e.g ., a sGFAP concentration of 170 pg/mL, or greater.
  • a measurement of sGFAP concentration e.g., of 170 pg/mL
  • the B cell depleting therapy administered to the subject when the subject has a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL or greater, may be a B cell depleting therapy.
  • a B cell depleting therapy may be anti-CD19 antibody such as VIB551 or a derivative thereof.
  • a B cell depleting therapy may be any therapy that depletes all or a select subset of B cells in the subject.
  • a B cell depleting therapy may be an anti-CD20 antibody such as Rituximab, Ocrelizumab or Ofatumumab.
  • a B cell depleting therapy may be an anti-CD22 antibody such as Epratuzumab.
  • a B cell depleting therapy may inhibit B Lymphocyte Stimulator (BLyS), such as Belimumab, BR3-Fc, AMG- 623, or Atacicept.
  • B Lymphocyte Stimulator B Lymphocyte Stimulator
  • the administration of the therapeutically effective amount of the B cell depleting therapy may thereby reduce NMOSD-related damage in the subject, reduce number of NMOSD-related attacks in the subject, reduce likelihood of NMQSD-related attacks in the subject, reduce likelihood of NMOSD-related attacks that are graded as major in severity in the subject, reduce the number of MRI lesions in the subject, reduce the rate of increase in new MRI lesions in the subject, reduce the worsening of EDSS score of the subject improve the subject’s EDSS
  • a method of reducing neuromyelitis optica spectrum disorder (NMOSD)- related damage in a patient at increased risk therefor comprising: identifying a patient as at increased risk for NMOSD-related damage, wherein the patient is identified as at increased risk if the patient comprises a serum glial fibrillary astrocytic protein (sGFAP) concentration of about. 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about.
  • sGFAP serum glial fibrillary astrocytic protein
  • the reducing NMOSD-related damage comprises reducing number of NMOSD-related attacks in the at increased risk patient relative to a baseline number of NMOSD-related attacks in the at increased risk patient, wherein the baseline number of attacks are determined over a first time period preceding the administering VIB551, wherein the number of attacks reduced by the administering VIB551 are determined over a second time period following the administering VIB551, and wherein the first and the second time period are of equal length.
  • reducing the NMOSD- related damage comprises reducing number of magnetic resonance imaging (MRI) lesions or reducing rate of increase in new MRI lesions in the at increased risk patient.
  • MRI magnetic resonance imaging
  • reducing the NMOSD- related damage comprises reducing rate of worsening of expanded disability status scale (EDSS) score, or improving EDSS score, of the at increased risk patient.
  • EDSS expanded disability status scale
  • a method of preventing NMQSD relapse in a patient diagnosed with NMOSD comprising: identifying the patient as a candidate for preventing NMOSD relapse, wherein the patient is identified as a candidate if the patient: comprises a sGFAP concentration of less than about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/rnL, about 172 pg/mL, about 173 pg/mL, about 174 pg/mL, about 175 pg/mL, about 176 pg/mL, or about 181 pg/mL; administering VIB551 to the candidate; and preventing relapse in the candidate.
  • a method of suppressing a NMOSD-related attack in a patient diagnosed with NMOSD comprising: identifying the patient as at-risk for an NMOSD-related attack, wherein the patient is identified as an at-risk patient if the patient comprises an increase in sGFAP concentration relative to baseline sGFAP concentration: administering a therapy to the at-risk patient, wherein the administering is performed at most one week following the identifying; and suppressing the NMQSD-related attack in the at-risk patient.
  • a method of treating NMQSD in a subject comprising administering a therapeutically effective amount of a B cell depleting therapy to the subject when the subject has a sGFAP concentration of about 160 pg/mL, about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL, or greater.
  • a method of reducing NMOSD-related disability in a patient, diagnosed with NMQSD comprising: identifying a patient as at increased risk for NMOSD-related disability, wherein the patient is identified as at increased risk if the patient has an increase in serum Neurofilament light chain (NfL) levels over a baseline level; and administering VIB551 to the patient.
  • NfL Neurofilament light chain
  • a method of reducing NMOSD-related disability in a patient diagnosed with NMQSD comprising administering V1B551 to a patient with an increase in serum Nil levels over a baseline level.
  • a method of treating NMQSD in a patient comprising: identifying a patient, as at increased risk for NMOSD-related disability, wherein the patient, is identified as at increased risk if the patient has an increase in serum Neurofilament light chain (NfL) levels over a baseline level, and administering VIB551 to the patient.
  • NfL serum Neurofilament light chain
  • a method of treating NMOSD in a patient comprising administering VTB551 to a patient with an increase in serum Nfl levels over a baseline level.
  • a method of treating a patient suspected of having NMOSD comprising: identifying a patient as having one or more NMOSD-related symptoms; identifying a patient as at increased risk for NMOSD-related disability, wherein the patient is identified as at increased risk if the patient has an increase in serum Neurofilament light chain (NfL) levels over a baseline level; and administering VIB551 to the patient.
  • NfL serum Neurofilament light chain
  • a method of treating NMOSD in a patient comprising a therapy to a patient with an increase in serum Nfl levels over a baseline level.
  • a method of treating a patient suspected of having NMOSD comprising administering a therapy to a patient with an increase in serum Nfl levels over a baseline level and one or more NMOSD-related symptoms.
  • sGFAP serum glial fibrillary astrocytic protein
  • the sGFAP concentration is at least about 165 pg/mL, about 166 pg/mL, about 167 pg/mL, about 168 pg/mL, about 169 pg/mL, about 170 pg/mL, about 171 pg/mL, about 172 pg/mL, or about 173 pg/mL or greater.
  • reducing NMOSD-related damage is determined by at least one of: (a) a reduction in a number of NMOSD-related attacks in the subject in need thereof after the administering as compared to a baseline number of NMOSD-related attacks in the subject in need thereof before the administering; or (b) a reduction in a number of NMOSD-related attacks in the subject in need thereof after the administering as compared to an otherwise comparable control subject lacking the administering.
  • reducing the NMOSD- related damage in the subject in need thereof comprises: (a) reducing a number of magnetic resonance imaging (MRI) lesions; (b) reducing rate of increase in new MRI lesions; or (c) both (a) and (b).
  • MRI magnetic resonance imaging
  • a method of preventing neuromyelitis optica spectrum disorder (NMGSD) relapse in a subject in need thereof comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject in need thereof thereby preventing NMOD8 relapse, wherein the subject in need thereof comprises a serum glial fibrillary acidic protein (sGFAP) concentration of about 165 pg/mL.
  • NMGSD neuromyelitis optica spectrum disorder
  • sGFAP concentration is about: 166 pg/mL, 167 pg/mL, 168 pg/mL, 169 pg/mL, 170 pg/mL, 171 pg/mL, 172 pg/mL, 173 pg/mL, or greater.
  • a method of suppressing a neuromyelitis optica spectrum disorder (NMOSD)- related attack in a subject diagnosed with NMOSD comprising: (a) identifying the subject as at-risk for an NMOSD-related attack, wherein the subject is identified as an at-risk subject if the subject comprises an increase in sGFAP concentration relative to a baseline sGFAP concentration; and (b) administering a therapeutic to the at-risk subject in an amount effective to suppress the NMODS -related attack, wherein the administering is performed at most one week following the identifying.
  • NMOSD neuromyelitis optica spectrum disorder
  • NMQSD neuromyelitis optica spectrum disorder
  • sGFAP serum glial fibrillary acidic protein
  • sGFAP concentration is about: 165 pg/rnL, 166 pg/mL, 167 pg/mL, 168 pg/mL, 169 pg/rnL, 170 pg/rnL, 171 pg/mL, 172 pg/mL, 173 pg/mL, or greater.
  • a method of reducing neuromyelitis optica spectrum disorder (NMOSD)- related disability in a subject in need thereof comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject in need thereof, thereby reducing the NMOSD-related disability, wherein the subject in need thereof comprises: (a) an increase in serum Neurofilament light chain (sNfL) levels over a baseline level of the subject in need thereof; or (b) an increase in sNfL levels over an otherwise comparable control subject.
  • NMOSD neuromyelitis optica spectrum disorder
  • a method of reducing neuromyelitis optica spectrum disorder (NMOSD)- related disability in a subject diagnosed with NMOSD comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject diagnosed with NMODS, wherein the subject diagnosed with NMODS comprises: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject diagnosed with NMQDS; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • sNfL serum Neurofilament light chain
  • a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof comprising: (a) identifying a subject in need thereof at increased risk for NMOSD-related disability as determined by: (i) an increased serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof; or (ii) an increased sNfL level over an otherwise comparable control subject; and (b) administering a composition that comprises Inebilizumab or a derivative thereof to the subject identified in (a), thereby treating the NMQDS.
  • sNfL serum Neurofilament light chain
  • a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject in need thereof, thereby treating the NMQDS, wherein the subject in need thereof comprises: an increased serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof; or (b) an increased sNfL level over an otherwise comparable control subject.
  • sNfL serum Neurofilament light chain
  • a method of treating a subject suspected of having neuromyelitis optica spectrum disorder comprising administering a composition that comprises Inebilizumab or a derivative thereof to the subject, wherein the subject comprises one or more NMODS-related symptoms and at least one of; (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • NMODS-related symptoms at least one of; (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • a method of treating a subject suspected of having neuromyelitis optica spectrum disorder comprising: (a) identifying a subject as having one or more NMOSD-related symptoms; (b) determining if the subject identified in (a) is at increased risk for NMOSD-related disability as determined by (i) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject identified in (a); or (ii) an increase in sNfL levels over an otherwise comparable control subject; and (c) administering a composition that comprises Inebilizumab or a derivative thereof to the subject determined to be at increased risk for NMOSD-related disability from (b).
  • NMOSD-related symptoms comprising: (a) identifying a subject as having one or more NMOSD-related symptoms; (b) determining if the subject identified in (a) is at increased risk for NMOSD-related disability as determined by (i) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject identified
  • a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof comprising administering a therapeutic in an amount effective to treat the NMODS in the subject in need thereof, wherein the subject in need thereof comprises: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject in need thereof; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • NMODS neuromyelitis optica spectrum disorder
  • a method of treating a subject suspected of having neuromyelitis optica spectrum disorder comprising administering a therapeutic to the subject suspected of having NMOSD, wherein the subj ect. suspected of having NMOSD cornpri ses one or more NMODS-related symptoms and at least one of: (a) an increase in serum Neurofilament light chain (sNfL) level over a baseline level of the subject suspected of having NMOSD; or (b) an increase in sNfL level over an otherwise comparable control subject.
  • NOSD neuromyelitis optica spectrum disorder
  • the therapeutic comprises one or more of Eculizumab, Satralizumab, Ublituximab, Ravulizumab, Rituximab, Azathioprine, Mycophenolate Mofetil, or a low dose corticosteroid.
  • Example 1 Design of a Clinical Trial to investigate VIB551 as a Treatment for NMOSD, and that Identified a Relationship Between sGFAP Levels and NMOSD Disease Activity
  • VIB551 was investigated as a treatment for NMOSD in a clinical trial referred to as the “N-MOmentum study”. Full details of the N-MOmentum study have been published (Cree B., et. al, Lancet, 2019;394(10206): 1352-1363). Briefly, the N-MOmentum study was an international, multicenter, randomized, double-blind, placebo-controlled phase 2/3 trial with an open-label extension phase (ClinicalTrials.
  • Eligible subjects were randomized (3:1) to intravenous VIB551 300 mg or placebo administered on days 1 and 15 of the randomized controlled period (RCP). All study participants received oral corticosteroids (prednisone 20 mg per day or equivalent) during the initial treatment period (days 1-14, tapering to day 21) to minimize risk of an attack immediately after the first VIB551 dose; other immunosuppressant use was not permitted during the RCP. Subjects continued in the RCP for up to 28 weeks or until the occurrence of an adjudicated attack, with study visits conducted on days 1, 8, 15, 29, 57, 85, 113, 155, and 197 of the RCP. After completing the RCP or following an adjudicated attack, subjects could enter an optional open-label VIB551 treatment period of at least 1 year.
  • Table 1 Participant Demographics and Characteristics at Baseline (Intent-to-Treat sGFAP Analysis set.
  • AQP4-IgG aquaporin-4-i mnunoglobulin G
  • EDSS Expanded Disability Status Scale
  • ITT intent-to-treat
  • N/A not applicable
  • MOG myelin oligodendrocyte glycoprotein
  • RRMS relapsing-remitting multiple sclerosis
  • SD standard deviation.
  • the primary endpoint was time to the onset of an adjudicated NMQ8D attack during the RCP.
  • An attack was defined as the presence of a new symptom(s) or worsening of an existing symptom(s) related to NMQSD that met at least one of the protocol-defined criteria for an attack upon neurological evaluation.
  • Study investigators evaluated potential attacks within 72 hours.
  • NMOSD attack severity was graded according to the opticospinal impairment scale (OPSIS) which characterizes attacks as minor or major on the basis of changes in domain- specific scores for neurological function at a subject’s attack assessment visit relative to the subject’s previous assessment.
  • OPSIS opticospinal impairment scale
  • sGFAP concentrations were analyzed from blood samples collected from participants during RCP study visits at baseline (day 1), day 15, day 29, day 57, day 85, day 113, day 155, and day 197, and during any assessment visit for new or worsening NMOSD symptoms.
  • CONSORT Consolidated Standards of Reporting
  • sGFAP concentration was determined by a single molecule array (Simoa) technology, using the Quanterix Simoa GFAP assay (Quanterix Cotporation, Lexington, MA, USA) with samples run according to manufacturer’ s instructions.
  • a total of 215 participants from the N-MOmentum study (including 198 AQP4 ⁇ IgG seropositive and 17 AQP4 seronegative) provided 1260 serial and NMOSD attack-related samples for sGFAP analysis.
  • Example 2 Baseline sGFAP Levels are Elevated in NMOSD Subjects Compared to RRMS Subjects and Healthy Donors
  • sGFAP concentration was 128.3 (92.0-181.2) pg/mL for participants with NMOSD compared with 71.3 (55.6-102.2) pg/mL for age- and sex-matched healthy donors and 97.5 (76.5-131.4) pg/mL for individuals with RRMS,
  • Two AQP4-IgG-seronegative participants one who was MOG-IgG seropositive had elevated baseline sGFAP levels (Fig. 2B).
  • Elevated sGFAP concentrations were defined by being >2 standard deviations (SD) above the healthy donor mean concentration (>170 pg/mL) according to established laboratory procedures (Marshall WJ, Bangert SK. Clinical Biochemistry: metabolic and clinical aspects. 2nd edition ed: Churchill Livingstone, 2008.).
  • Example 3 NMOSD Subjects with Elevated Baseline sGFAP Levels Are at Increased Risk of an NMOSD Attack
  • Example 4 VIB551 Reduces Risk of NMOSD-Related Attacks in NMOSD Subjects, Regardless of Baseline sGFAP Level
  • VIB551 therapy was associated with a decreased risk of adjudicated attack in subjects with NMOSD.
  • the risk of an adjudicated attack was reduced by 79% with VIB551 compared with placebo (HR [95% Cl] 0.21 [0.08—0.51 ]; P ⁇ .001; Fig. 4E).
  • Example 5 sGFAP Levels increase Within One Week of an NMOSD-Related Attack
  • Elevated sGFAP concentration was also associated with the severity of the adjudicated NMQSD attack.
  • sGFAP concentrations tended to be higher during major adjudicated attacks compared with minor adjudicated attacks across all domains, including attacks that only affected the optic nerve (Fig. 6B). This trend was consistent in both the VTB551 and placebo treatment groups (Fig. 7 A- Fig. 7D).
  • Example 1% VIB551 Decreases sGFAP Levels in Attack-Free NMOSD Subjects
  • sGFAP concentrations decreased with VIB551 treatment after week 4.
  • the reduction from baseline was statistically significant from week 16 (median [IQR] reduction of 12.9 [-25.6, — 1.6] %) to the end of the RCP (P ⁇ .05; Fig. 8C).
  • IQR index of 12.9 [-25.6, — 1.6]
  • sGFAP concentrations decreased with VIB551 treatment after week 4.
  • the reduction from baseline was statistically significant from week 16 (median [IQR] reduction of 12.9 [-25.6, — 1.6] %) to the end of the RCP (P ⁇ .05; Fig. 8C).
  • Example 8 Even in NMOSD Subjects That Did Not Experience an NMOSD-Related Attack, an Increase in sGFAP Concentration Indicated an Increase in NMOSD Disease Activity [0252] Among the 161 participants without an attack, 18 (11.2%) displayed an increase greater than twofold in sGFAP concentration in at least one sample draw. These increases from baseline were comparable to the range observed in subjects with attacks (Fig. 9 A) and well outside the variation observed in longitudinal draws from healthy donors (Fig. 9B). Five of these 18 participants (28%) with an elevation in sGFAP reported neurological symptoms that were rated as attacks by the treating investigators but not confirmed by the adjudication committee (AC). Of note, for the total cohort of these 18 participants, increased rate of adverse events was observed in temporal vicinity to sampling (Table 7).
  • Table 7 Overview of Adverse Event and Severe Adverse Events in Attack-Free Subjects with sGFAP Increases
  • Example 8 AQP4 ⁇ IgG seronegative subjects
  • AQP4 an autoantibody against aquaporin-4 (AQP4), a water channel expressed on astrocytes, is detected in up to 90% of subj ects with NMOSD ( ⁇ Jarius S and Wildemann B , Nat Rev Neurol 2010;6:383-92,)
  • AQP4-IgG is produced by CD19 positive (CD 19+) B-lineage plasmablasts, and the presence of these plasmablasts correlates with disease activity in NMO (Chihara N, et al. Proc Natl Acad Sci USA 2011; 108(9) : 3701 - 6 , Kirn W, et al. J Clin Neurol 2011;7(3):115- 27. Greenberg BM, et al.
  • Fig, 11 shows the AQP4-IgG seropositive vs. AQP4- IgG seronegative subgroup. As can be seen there is a higher proportion of male subjects and a greater baseline disability based on F.DSS in the seronegative subgroup.
  • AQP4-IgG seronegative subjects had AC-determined NMQ/NMOSD attacks during the RCP. All 3 attacks in AQP4-IgG seronegative subjects were in the Inebilizumab-treated group and occurred in the first 3 months of the RCP. There were no observed attacks in the remaining 10 Inebilizumab-treated or 4 placebo-treated AQP4-IgG seronegative subjects through the first 6 months of the OLP.
  • Fig. 13 shows the annualized attack rates during RCP (post hoc analysis) for AQP4-IgG seronegative subjects.
  • the AAR for the RCP was 0.09 (95% Cl: 0.02-0.26), with a similar decline in ARR observed in MOG-IgG1 seropositive and MOG-IgGl seronegative subjects.
  • the N- MOmentum trial provided clinically important insight on the difficulty of correctly diagnosing AQP4- NMQSD and suggests that Inebiiizumab may have a benefit on AAR in these subjects.
  • Example 9 Seram neurofilament light chain levels (sNfl) correlate with attack-related disability in neuromyelitis optica
  • NMQSD neuromyelitis optica spectrum disorder
  • astroglial and neuronal proteins such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxyl -terminal hydrolase LI (UCH-L1) and Tau into the circulation.
  • NMO8D NfL, 16%; U C H -LI, 6%, Tau, 12%; sGFAP, 29%)
  • RRMS relapsing-remitting multiple sclerosis
  • sGFAP baseline-controlled regression analysis demonstrated that biomarkers other than sGFAP were not independently associated with attack risk.
  • Cox regression analysis controlling for sGFAP concentration levels revealed that markers other than sGFAP were not independently associated with increased attack risk (hazard ratios ⁇ 2, p>0.05).
  • NfL correlated with EDSS score at attack assessments (R, 0.55; p ⁇ 0.001); other biomarkers did not correlate with EDSS after controlling for NfL levels.
  • sNfL at attack is strongest correlate of EDSS change at attack follow-up (EDSS assessment and serum sample draw performed within 7 days of attack).
  • serum NfL, UCH-L1 and Tau levels were higher than in HC; increased baseline sGFAP levels were associated with a greater risk of attack. While GFAP levels showed the greatest increase following attacks, NfL correlated with attack-related disability.

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WO2025139632A1 (zh) * 2023-12-29 2025-07-03 广州赛莱拉干细胞科技股份有限公司 人乳脂球表皮生长因子8用于制备治疗视神经脊髓炎谱系疾病药物中的应用

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WO2025139632A1 (zh) * 2023-12-29 2025-07-03 广州赛莱拉干细胞科技股份有限公司 人乳脂球表皮生长因子8用于制备治疗视神经脊髓炎谱系疾病药物中的应用

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