Uplizna (inebilizumab-cdon)

P4, N=80, Not yet recruiting, The Third Affiliated Hospital, Sun Yat-sen University; The Third Affiliated Hospital, Sun Yat-sen University

P=N/A, N=60, Recruiting, Amgen | Trial completion date: Aug 2032 --> Oct 2032 | Trial primary completion date: Aug 2032 --> Oct 2032

P=N/A, N=0, Available, Amgen

P=N/A, N=50, Recruiting, Xuanwu Hospital, Beijing | Not yet recruiting --> Recruiting

P4, N=128, Recruiting, West China Hospital,Sichuan University; West China Hospital,Sichuan University

P2, N=50, Not yet recruiting, Amgen

P3, N=80, Recruiting, Mitsubishi Tanabe Pharma Corporation | Trial completion date: Jul 2026 --> Apr 2027 | Trial primary completion date: Jun 2024 --> Mar 2025

P4, N=30, Recruiting, Horizon Therapeutics Ireland DAC | Not yet recruiting --> Recruiting

In 2019, several randomized, placebo-controlled trials were completed that demonstrated the remarkable efficacy of eculizumab (anti-C5 complement inhibitor), inebilizumab (anti-CD19 B-cell-depleting agent), and satralizumab (anti-interleukin-6 receptor), leading to the Food and Drug Administration (FDA) approval of specific treatments for AQP4-IgG+NMOSD for the first time. Most recently, ravulizumab (anti-C5 complement inhibitor) was also shown to be highly efficacious in an open-label, external-controlled trial...Observational studies showed that tocilizumab was associated with a decrease in relapses, whereas rituximab seemed to have less robust effectiveness in MOGAD compared to AQP4-IgG+NMOSD. Herein, we review the evidence on the efficacy and safety of each monoclonal antibody therapy used in AQP4-IgG+NMOSD and MOGAD, including special considerations in children and women of childbearing potential.

P4, N=33, Not yet recruiting, Hansoh BioMedical R&D Company

Compared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo.

In this study, we developed a Volasertib antibody-drug conjugate (V-ADC) using -CD19 antibody Inebilizumab to increase the targeting specificity for B-cell lymphoma cells and minimize the side effects of Volasertib. In conclusion, starvation and lysosomal cathepsin activation increased V-ADC-induced apoptotic cell death in CD19 overexpression Z138 cell lines. We are actively investigating the in vivo therapeutic effects of V-ADC in patient-derived xenograft (PDX) animal models of MCL and other aggressive B-cell lymphomas.

While there have been no studies on the safety of ICIs in NMOSD patients, there was a case reported of newly-diagnosed NMOSD following nivolumab treatment...Design/Methods Case report Results A 66-year-old woman with AQP4-IgG+ NMOSD, diagnosed in 2015 and treated with inebilizumab, was diagnosed with metastatic SCC of the tongue in February 2022...Conclusions An NMOSD attack occurred rapidly following pembrolizumab in a B-cell depleted patient, suggesting a role for T cell activation in relapse. ICIs should be used with caution in NMOSD patients.

Effective rescue therapy for acute attack is critical given permanent disability in NMOSD is attack-related, and biologic agents that treat acute attack are emerging. If such treatments are to become widely applied, studies on the most cost-effective treatment strategies are needed.

Currently, NMOSD poses both diagnostic and treatment challenges. It is debated whether individuals who are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG belong within the neuromyelitis optica spectrum. This discussion is fueled by disparities in treatment responses between patients who are AQP4-IgG seropositive and seronegative, suggesting different immunopathologic mechanisms may govern these conditions. As our understanding regarding the immune pathophysiology of NMOSD expands, emerging biomarkers, including serum neurofilament light chain and glial fibrillary acidic protein (GFAP), may facilitate earlier relapse detection and inform long-term treatment decisions. Future research focal points should include strategies to optimize relapse management, restorative treatments that augment neurologic recovery, and practical solutions that promote equitable access to approved therapies for all patients with NMOSD.

The most common treatments used for relapses are steroids and plasma exchange.Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19 B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.

Treatment of antibody-mediated encephalomyelitis differs from treatment of multiple sclerosis and requires specific measures.

NK cells over-expressing miR-629 also showed a decreased killing capacity in ADCC assays with cetuximab and trastuzumab, as shown with Inebilizumab.Together, this work reveals a role for miR-629 in altering NK function and highlights the potential to use miR-629 as a biomarker of response to ADCC-mediated therapeutics across multiple cancer indications. More detailed analyses of clinical outcome with miR-629 expression in larger trials will be necessary to confirm these results.