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By Brian Hoyle VIRTUAL -- May 5, 2021 -- A novel N-methyl-d-aspartate (NMDA)-negative allosteric modulator dubbed MIJ821 appears safe and effective in patients with treatment-resistant depression, according to a study presented at the Virtual 2021 Meeting of the American Psychiatric Association (APA). “In this proof-of-concept study, MIJ821 was associated with a significant improvement in MADRS [Montgomery-åsberg Depression Rating Scale] score versus placebo in patients with treatment-resistant depression,” said Nassir Ghaemi, MD, Novartis Institute for Biomedical Research, and Harvard Medical School, Cambridge, Massachusetts. “No new safety signals were identified.” The study included 70 patients with treatment-major depressive disorder and prior failure of ≥2 standard antidepressants of adequate dose and >8 weeks duration in a major depressive episode, and Montgomery-åsberg Depression Rating Scale (MADRS) score ≥24. Patients were randomised to receive 40-minute intravenous infusions of low-dose MIJ821 once weekly (n = 11), low-dose MIJ821 biweekly (n = 10), high-dose MIJ821 weekly (n = 10), high-dose MIJ821 biweekly (n = 9), weekly ketamine (n = 10), or weekly placebo (n = 20). Patients were followed for 4 weeks after completion of the infusion schedule. The primary endpoint was 24-hour change from baseline in MADRS score. Mean MADRS score decreased by 15.51 points in the pooled (with respect to weekly or biweekly infusion) low-dose MIJ821 groups, 12.98 in the similarly pooled high-dose MIJ821 groups, 12.94 in the ketamine group, and 7.27 in the placebo group. At 24 hours, adjusted mean differences versus placebo were -8.25 (P = .0013) in the pooled low-dose MIJ821 groups, -5.71 (P = .0196) in the pooled high-dose MIJ821 groups, and -5.67 (P = .0461) in the ketamine group. At 48 hours, the respective results were -7.06 (P = .0130), -7.37 (P = .0133), and -11.02 (P = .0199). At 6 weeks, the adjusted mean differences in MADRS scores compared with placebo were -5.78 (P = .0427) for low-dose MIJ821, -4.24 (P = .1133) for high-dose MIJ821, and -5.01 (P = .0439) for ketamine. At 24 hours, 48 hours, and 6 weeks, the change in Clinical Global Impression-Improvement score compared with placebo was 10.0%, 10.5%, and 17.7%, respectively. The most consistent improvement versus placebo was evident for the biweekly regimen with the low dose of MIJ821 (40%, 30%, and 50%, respectively). Rates of adverse events (AEs) were similar across groups. The most common AEs in the MIJ821 groups included amnesia, dissociation, sedation, and vomiting. “The potentially low rate of psychotomimetic side effects with MIJ821 is an advantage over ketamine in patients with treatment-resistant depression,” said Dr. Ghaemi. “Subsequent studies will determine whether the success of the current proof-of-concept study holds. These results will spur phase 3 scrutiny of the long-term treatment efficacy, which has been elusive until now in patients with depression that has not been addressed by other treatments.” [Presentation title: Efficacy and Safety of MIJ821 in Patients With Treatment-Resistant Depression: Results From a Randomized, Placebo-Controlled, Proof-of-Concept Study. Abstract P10-009] |
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