Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis Optica Spectrum Disorder)

Abstract

: Inebilizumab-cdon (Uplizna™) was currently approved by the United States Food and Drug Administration (USFDA) for the treatment of NMOSD (neuromyelitis optica spectrum disorder). It was developed by Viela Bio (Nasdaq: VIE) USA. Inebilizumab-cdon (formerly MEDI-551) is a humanized antibody, which induces CD19 + B cell depletion by increasing antibody-dependent cell cytotoxicity (ADCC) and cell phagocytosis (ADCP) of effector cells. Various clinical trials exhibit its safe and effective pharmacokinetic and pharmacodynamic profile. In June 2019, Viela Bio submitted Biologics License Application (BLA) to the FDA based on the findings obtained from the N-Momentum trial. This article summarizes the milestones in the development of Inebilizumab-cdon leading to approval for the treatment of advanced NMOSD.

Intruders or protectors – the multifaceted role of B cells in CNS disorders

“…IL-6 is elevated in the serum of patients with NMO ( Uzawa et al, 2010 ; Barros et al, 2016 ) and is positively correlated with disease severity ( Matsushita et al, 2013 ) and AQP4-IgG levels ( Uzawa et al, 2010 ). Inebilizumab-cdon has recently gained FDA approval for treatment of NMO ( Ali et al, 2022 ). It targets CD19, largely expressed in B lineage cells which differs from rituximab in that it can deplete plasma cells, which express CD19, but not CD20.…”

“…This reduces AQP4-ab production ( Bennett et al, 2015 ). Afucosylation of Inebilizumab-cdon results in almost 10-fold greater affinity for the FcγRIIIA receptor ( Yan et al, 2022 ), key in regulating antibody-dependent cellular cytotoxicity and antibody-dependent phagocytosis ( Tullman et al, 2021 ; Ali et al, 2022 ). The effectiveness of these therapies in reducing AQP4-ab mediated astrocyte destruction, either through inhibiting plasma cell proliferation or directly altering the effects of AQP4-abs demonstrates the prominent role of B cells in NMO pathogenesis.…”

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

“…Prior to the approval of monoclonal antibody therapy, unapproved methods for preventing recurrence mainly relied on medications like rituximab and azathioprine [14] . Rituximab, a human/mouse chimeric monoclonal antibody, specifically targets the CD20 antigen on the surface of B lymphocytes, triggering B lymphocyte lysis through immune responses [15][16] . Mechanisms underlying cell lysis include complementdependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC).…”

Review of Satralizumab for Neuromyelitis Optica Spectrum Disorder: A New Biologic Agent Targeting the Interleukin-6 Receptor

“…Eculizumab monoclonal antibody targeting C5 complement protein was the first therapy approved by the USFDA for NMOSD in AQP4 antibody-positive adult patients [23]. Inebilizumab, which is a humanized monoclonal targeting B cellspecific antigen CD19, was the second drug to be approved therapy by the USFDA to use in adult patients with NMOSD who are found to be anti-aquaporin-4 or AQP4 antibody positive) [24]. Satralizumab was approved in 2020 and was the third monoclonal antibody after eculizumab and inebilizumab to receive the nod from the USFDA for treating NMOSD [25].…”