Sensitivity analyses of time to adjudicated attacks in the N-MOmentum study: P1652 a randomized, placebo-controlled, double-masked trial in patients with neuromyelitis optica spectrum disorder Bruce AC Cree,1 Jeffrey L Bennett,2 Ho Jin Kim,3 Brian Weinshenker,4 Sean J Pittock,4 Dean Wingerchuk,5 Kazuo Fujihara,6 Friedemann Paul,7 Gary Cutter,8 Romain Marignier,9 Ari Green,10 Orhan Aktas,11 Hans-Peter Hartung,11 Fred D Lublin,12 Maureen A Mealy,13 Jorn Drappa,13 Gerard Barron,14 Soraya Madani,13 Dewei She,13 Daniel Cimbora,13 William Rees,13 John N Ratchford13 and Eliezer Katz,13 on behalf of the N-MOmentum Study Investigators 1UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; 2University of Colorado, School of Medicine, Anschutz Medical Campus, Aurora, CO, USA; 3Research Institute and Hospital of the National Cancer Center, Seoul, South Korea; 4Mayo Clinic, Rochester, MN, USA; 5Mayo Clinic, Scottsdale, AZ, USA; 6Department of Multiple Sclerosis Therapeutics, Fukushima Medical University and Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan; 7Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany; 8University of Alabama at Birmingham, Birmingham, AL, USA; 9Lyon University Hospital, Lyon, France; 10UCSF Weill Institute for Neurosciences, Department of Neurology and Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; 11Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; 12Icahn School of Medicine at Mount Sinai, New York, NY, USA; 13Viela Bio, Gaithersburg, MD, USA; 14Viela Bio, Cambridge, UK INTRODUCTION Figure 3. Sensitivity and subset analyses for primary variable (time to adjudicated attack; overall population) • Neuromyelitis optica spectrum disorder (NMOSD) is a severe, Number of patients with an attack autoimmune, inflammatory disease of the central nervous system Sensitivitysubset analysis Placebo Inebilizumab HR (95 CI) p value Favours inebilizumab Favours placebo (n 56) (n 174) characterized by repeated attacks of optic neuritis, transverse Number of patients with an attack -determined NMOSD attacs 22 () 21 (121) 22 (1–) 1 myelitis or brain/brainstem encephalitis, which causes disability Sensitivitysubset analysis Placebo Inebilizumab HR (95 CI) p value Favours inebilizumab Favours placebo 1 (primary analysis) or death. (n 56) (n 174) • N-MOmentum is a prospective, randomized, placebo-controlled, nanimous decisions 1 (21) 1 (2) 2 (12–) 1 -determinednvestigator-determined NMOSD attacsattacs 222 (11)() 221 (1)(121) 222 (1–) 1 double-masked trial of inebilizumab, an anti-CD19 monoclonal (primary analysis) 2 atient-reported attacs 2 () (1) (2–) 0.0004 B-cell-depleting antibody, in patients with NMOSD. nanimous decisions 1 (21) 1 (2) 2 (12–) 1 ttacs including patients o 22 () 2 (1) (11–) 2 • In N-MOmentum the risk of an adjudicated NMOSD attack was nvestigator-determinedprematurely discontinued attacs te study 2 (11) 2 (1) 2 (1–) 1 significantly reduced with inebilizumab compared with placebo.2 atient-reportedttacs ased on attacs only clinical criteria 12 () 1 (1) 2 (1–)(2–) 10.0004 ttacsand not includingreuiring patientsM conirmation o 22 () 2 (1) (11–) 2 OBJECTIVE prematurelyomined attacs discontinued or use ote study 2 () 2 (1) 2 (11–) 1 • To assess the robustness of the primary endpoint in N-MOmentum, ttacsrescue terapy ased on only clinical criteria 1 () 1 (1) 2 (1–) 1 and not reuiring M conirmation the time to an adjudicated NMOSD attack, using pre-planned Optic neuritis attacs 1 (1) 1 () 2 (12–) 0.0055 ominedSpinal cord attacs attacs or use o 21 () (2) 21 (1)() 222 (12–)(11–) 0.00051 sensitivity and subset analyses. rescue terapy Optic neuritis attacs 1 (1) 1 () 2 (12–) 0.0055 0.0 0.5 1 1 METHODS Spinal cord attacs 1 (2) 1 () 22 (12–) 0.0005 aard ratio Study design Based on Cox regression method, with placebo as the reference group. AC, adjudication committee; CI, confidence interval; HR, hazard ratio; MRI, magnetic resonance imaging. 0.0 0.5 1 1 Number of patients with an attack • Adults with NMOSD and an Expanded Disability Status Scale aard ratio Placebo Inebilizumab score of ≤ 8 were randomly assigned (3:1) to receive intravenous FigureSensitivitysubset 4. Sensitivity analysis and subset analyses for primary variable (time to HRadjudicated (95 CI) attack; pAQP4-IgG value seropositiveFavours inebilizumab population) Favours placebo (n 52) (n 161) inebilizumab 300 mg or placebo on days 1 and 15, with no other Number of patients with an attack treatments allowed (Figure 1). -determined NMOSD attacs 22 (2) 1 (112) 22 (121–2) 1 Sensitivitysubset(primary analysis) analysis Placebo Inebilizumab HR (95 CI) p value Favours inebilizumab Favours placebo – Participants could be aquaporin 4 (AQP4)-IgG seropositive or (n 52) (n 161) nanimous decisions 1 () 1 () 2 (12–) 1 seronegative. nvestigator-determined-determined NMOSD attacsattacs 222 (2)(2) 221 (1)(112) 2222 (1–)(121–2) 1 • The randomized controlled period was 28 weeks or up to an (primary analysis) atient-reported attacs 2 (1) (1) (2–) 2 adjudicated attack. nanimous decisions 1 () 1 () 2 (12–) 1 ttacs including patients o 22 (2) 22 (1) 2 (12–) 1 – Attacks were evaluated using predefined attack diagnosis prematurelynvestigator-determined discontinued attacs te study 2 (2) 22 (1) 22 (1–) 1 criteria, which were developed specifically for this study. ttacsatient-reported ased on attacs only clinical criteria 12 ()(1) 1 (1)() 21 (2–)(11–) 12 – Each attack was assessed by study investigators and an andttacs not includingreuiring patientsM conirmation o 22 (2) 22 (1) 2 (12–) 1 independent adjudication committee (AC) composed of ominedprematurely attacs discontinued or use ote study 2 (2) 2 (1) 2 (1–) 1 three members. rescuettacs terapy ased on only clinical criteria 1 () 1 () 21 (11–) 1 • Only attacks confirmed by an AC majority (2/3) were used for the Opticand not neuritis reuiring attacs M conirmation 1 (12) () 222 (–) 1 primary endpoint analysis. Spinalomined cord attacs attacs or use o 12 (2)(2) 211 (1)() 212 (–2)(1–) 1 • Sensitivity and subset analyses were performed to assess whether rescue terapy the primary endpoint remained significant when considering Optic neuritis attacs 1 (12) () 222 (–) 1 0.0 0.5 1 1 aard ratio attacks as reported by unanimous AC decisions, by investigators or Spinal cord attacs 1 (2) 11 () 21 (–2) 1 by patients. 0.0 0.5 1 1 • Subsets of the primary endpoint defined by attack type or aard ratio the inclusion of patients who discontinued prematurely were also assessed. Based on Cox regression method, with placebo as the reference group. AC, adjudication committee; AQP4-IgG; aquaporin 4 immunoglobulin G; CI, confidence interval; HR, hazard ratio; MRI, magnetic resonance imaging. Figure 1. N-MOmentum study design RESULTS CONCLUSIONS Day 1 Day 1 300 mg 300 mg • In N-MOmentum, inebilizumab consistently provided a statistically Participants Day 15 Day 15 significant reduction in the risk of attacks compared with placebo, 300 mg Placebo • Of the 467 participants screened, 230 were randomized and dosed, regardless of who evaluated or reported attacks, whether decisions with 175 randomly assigned to inebilizumab (with one patient not were based on only clinical criteria, and also when considering dosed) and 56 to placebo (overall population). individual attack types separately. – In the subset of patients who were AQP4-IgG seropositive, Inebilizumab • These results confirm the robustness of the primary endpoint in the 3 161 were randomized to inebilizumab and 52 to placebo. Open-label N-MOmentum study in both the AQP4-IgG seropositive and the Screening perioda ≥ 1 year • Baseline demographics and characteristics were generally 28 days : RCP – 197 days overall populations. 300 mg inebilizumab Primary endpoint: time to similar between treatment groups in the overall population and in every 6 months 1 NMOSD attack AQP4-IgG seropositive participants. References 1. Cree BAC et al. Mult Scler 2016;22:862–72. Placebo Primary analysis of time to adjudicated attacks 2. Cree BAC et al. Lancet. Forthcoming, September 2019. • According to majority AC decision, 21/174 patients (12.1%) who Acknowledgements Day 15 Day 15 received inebilizumab and 22/56 (39.3%) who received placebo The investigational biological product discussed in this poster (inebilizumab) has not been approved Placebo 300 mg or licensed by the US Food and Drug Administration or by any other regulatory authority, and it is not commercially available in any market. Medical writing support was provided by Oxford PharmaGenesis, experienced attacks. Oxford, UK. This data presentation is sponsored by Viela Bio. Day 1 Day 1 Placebo 300 mg – The risk reduction for inebilizumab versus placebo was 72.8%; hazard ratio, 0.272 (95% confidence interval, 0.150–0.496), Disclosures aPatients eligible for the open-label period at the end of the RCP or after an adjudicated attack. BAC Cree has received personal compensation for consulting from AbbVie, Akili, Alexion, Biogen, N-MOmentum was a double-masked, placebo-controlled study at 99 medical centres in 25 countries, with p < 0.0001 (Figure 2). GeNeuro, EMD Serono, Novartis, Sanofi Genzyme and TG Therapeutics. JL Bennett reports payment a time-to-event design. End of RCP was defined as 67 NMOSD attacks, or when 252 patients had been for study design/consultation from MedImmune/Viela Bio; personal fees from AbbVie, Chugai, Clene randomized and had received study drug, whichever happened first. Enrolment was stopped early at 231 Sensitivity and subset analyses of time to adjudicated attack Nanomedicine, Equillium, Frequency Therapeutics, Genentech, Genzyme and Alexion; grants and patients and 43 attacks due to proven efficacy as determined by the IDMC. No background immunotherapy personal fees from EMD Serono and Novartis; grants from the Guthy–Jackson Charitable Foundation, was permitted. Primary endpoint was the time to NMOSD adjudicated attack within the RCP. Mallinckrodt and the National Institutes of Health; and has a patent for Aquaporumab issued.