Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study.

BACKGROUND

Inebilizumab, an anti-CD19 B cell-depleting antibody, reduced the risk of a neuromyelitis optica spectrum disorder (NMOSD) attack, disability worsening, magnetic resonance imaging (MRI) lesion activity, and disease-related hospitalizations in participants with NMOSD in the N-MOmentum study (NCT02200770). However, the efficacy and safety outcomes of inebilizumab specific to an Asian population were not fully reported. Therefore, subgroup analyses of the N-MOmentum study were conducted post hoc to evaluate the efficacy and safety of inebilizumab in Asian participants with NMOSD.

METHODS

The N-MOmentum study was a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial with an open-label extension period (OLP). In the subgroup analyses, data from Asian participants from the N-MOmentum study were compared with those of non-Asian participants. Eligible participants were randomly allocated (3:1) to receive 300 mg intravenous (IV) inebilizumab or placebo on Days 1 and 15. Participants who had an NMOSD attack or completed the randomized controlled period (RCP) could enter the OLP, where they received inebilizumab for ≥2 years. All participants who entered the OLP received inebilizumab 300 mg IV every 6 months.

RESULTS

Overall, 230 participants received treatment (174 received inebilizumab and 56 received placebo), of whom 47 were Asian (39 received inebilizumab and 8 received placebo). Baseline characteristics were similar between the Asian and non-Asian subgroups, except for disease duration, annualized relapse rate prior to randomization in this study, and previous maintenance therapy. In the Asian subgroup, the risk of NMOSD attacks was reduced with inebilizumab versus placebo (hazard ratio, 0.202) and the attack-free rate at 28 weeks was 82.1% with inebilizumab versus 37.5% with placebo, in the 6-month RCP. NMOSD attack rates were comparable between the Asian and non-Asian subgroups. In the Asian subgroup, the rates of Expanded Disability Status Scale worsening from baseline, active MRI lesions, and disease-related hospitalizations tended to be lower in the inebilizumab group than in the placebo group; similar results were shown in the non-Asian subgroup. For long-term efficacy and safety (RCP and OLP), the annualized adjudicated NMOSD attack rate in Asian participants treated with inebilizumab was reduced (0.096) compared with that at baseline (1.04), with a mean follow-up period of inebilizumab treatment of 3.38 years, which was consistent with the results in the non-Asian subgroup. The risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizumab/inebilizumab and placebo/inebilizumab groups in the Asian and non-Asian subgroups. The incidence of treatment-emergent adverse events (TEAEs) was similar between the Asian and non-Asian subgroups. In the Asian and non-Asian subgroups, 15.2% and 35.2% of participants, respectively, had at least one serious TEAE and/or Grade ≥3 TEAE during long-term therapy. No deaths occurred in the Asian subgroup whereas three deaths occurred in the non-Asian subgroup.

CONCLUSION

Inebilizumab reduced the risk of an NMOSD attack, progression of disability, MRI lesion activity, and disease-related hospitalizations in Asian participants with NMOSD. The efficacy of inebilizumab in reducing NMOSD attacks continued without any unexpected safety signals or concerns during long-term use in Asian participants.

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Employees of MedImmune and Viela Bio (now Horizon Therapeutics) participated in the design and conduct of the study; and data collection, management, analysis, and interpretation. Kazuo Fujihara has received grants or contracts from the Ministry of Health, Labour and Welfare Japan; consulting fees from Merck Biopharma, Japan Tobacco Inc, and AbbVie; and payment or honoraria for lectures, presentations, manuscript writing, or educational events from Viela Bio/MedImmune, Biogen, Mitsubishi Tanabe Pharma, Novartis Pharma, Chugai Pharmaceutical, Eisai, Asahi Kasei Medical, Merck, and Takeda Pharmaceutical; has participated in a data safety monitoring board or advisory board of VielaBio/Horizon Therapeutics, Mitsubishi Tanabe Pharma, Novartis Pharma, Chugai Pharmaceutical, Alexion Pharmaceuticals, Biogen, and UCB; and has a leadership or fiduciary role in Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), Japanese Society of Neuroimmunology, Japan Multiple Sclerosis Society, and European Charcot Foundation. Ho Jin Kim has received grants or contracts from the National Research Foundation of Korea, Aprilbio, Eisai, and UCB; consulting fees from Altos Biologics, Biogen, Daewoong Pharmaceutical, Handok, Horizon Therapeutics (formerly Viela Bio), Kaigene, Kolon Life Science, Mdimune, Merck, Roche, Sanofi Genzyme, and UCB; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Biogen, Eisai, GC Pharma, Merck, Mitsubishi Tanabe Pharma, Roche, and Sanofi Genzyme. Takahiko Saida has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Biogen, Eisai, Mitsubishi Tanabe Pharma, and Novartis Pharma. Tatsuro Misu has received grants or contracts from Cosmic Corporation and Medical and Biological Laboratories Co.; and speaker honoraria from Biogen Idec, Mitsubishi Tanabe Pharma, Novartis Pharma, Chugai Pharmaceutical, Alexion Pharmaceuticals, Teijin Pharma., and Viela Bio. Yoshito Nagano, Naoko Totsuka, Masato Iizuka, Shinsuke Kido, Ryuuji Terata, Kyoko Okumura, and Shinya Hirota are employees of Mitsubishi Tanabe Pharma Corporation. Bruce A. C. Cree has received grants or contracts from Genentech; consulting fees from Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Neuron23, Novartis, Sanofi, Siemens, TG Therapeutics, and Therini; has participated in a data safety monitoring board or advisory board of Immunic AG; and has stock options in Autobahn.