Poster
118
(#118) Impact of AXS-12 on Symptom Severity and Functional Impairment in Narcolepsy: Results from the Phase 3 SYMPHONY Trial
Psych Congress 2025
Abstract: Introduction
AXS-12 (reboxetine) is a selective norepinephrine reuptake inhibitor and cortical dopamine modulator under investigation for narcolepsy. In the Phase 3 SYMPHONY study, AXS-12 met the primary endpoint, significantly reducing weekly cataplexy attack frequency versus placebo. We report secondary endpoints assessing symptom severity, daily functioning, and mood.
Methods
SYMPHONY was a randomized, double-blind, placebo-controlled study in patients with narcolepsy type 1. Participants (15-75 years) were randomized to AXS-12 or placebo for 5 weeks. Secondary endpoints included the Clinical Global Impression of Severity (CGI-S) for narcolepsy, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) anxiety/depression domain.
Results
Ninety participants were enrolled. Baseline mean (SD) CGI-S for narcolepsy scores were 5.2 (1.0) for AXS-12 and 4.9 (1.0) for placebo. At week 5, AXS-12 significantly improved CGI-S versus placebo (LS mean difference [95% CI]=0.72 [0.29, 1.16]; p=0.001). Baseline mean FOSQ-10 total scores were 11.1 (3.1) for AXS-12 and 11.6 (3.2) for placebo. At Week 5, AXS-12 significantly improved FOSQ-10 score versus placebo (LS mean difference [95% CI]=1.66 [0.51, 2.82]; p=0.005). At baseline, 47.8% of participants in the AXS-12 arm and 45.5% in the placebo arm reported anxiety/depression (EQ-5D-5L); numerically more participants improved ≥1 level with AXS-12 (55.0%) versus placebo (31.6%) at Week 5 (p=0.146).
Conclusions
AXS-12 demonstrated a reduction in clinical impression of overall narcolepsy symptom severity, functional impairment due to EDS, and improved mood-related symptoms. Combined with prior findings, these results highlight the potential of AXS-12 to address narcolepsy symptoms affecting quality of life and functioning.
Short Description: AXS-12 (reboxetine) is a selective norepinephrine reuptake inhibitor and cortical dopamine modulator under investigation for narcolepsy. In the Phase 3 SYMPHONY study, AXS-12 significantly reduced cataplexy frequency. Here we report results from secondary endpoints, which show AXS-12 reduced the clinical impression of overall narcolepsy symptom severity, functional impairment due to excessive daytime sleepiness, and improved mood-related symptoms. These results highlight the potential for AXS-12 to address narcolepsy symptoms affecting quality of life and function.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc.
AXS-12 (reboxetine) is a selective norepinephrine reuptake inhibitor and cortical dopamine modulator under investigation for narcolepsy. In the Phase 3 SYMPHONY study, AXS-12 met the primary endpoint, significantly reducing weekly cataplexy attack frequency versus placebo. We report secondary endpoints assessing symptom severity, daily functioning, and mood.
Methods
SYMPHONY was a randomized, double-blind, placebo-controlled study in patients with narcolepsy type 1. Participants (15-75 years) were randomized to AXS-12 or placebo for 5 weeks. Secondary endpoints included the Clinical Global Impression of Severity (CGI-S) for narcolepsy, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) anxiety/depression domain.
Results
Ninety participants were enrolled. Baseline mean (SD) CGI-S for narcolepsy scores were 5.2 (1.0) for AXS-12 and 4.9 (1.0) for placebo. At week 5, AXS-12 significantly improved CGI-S versus placebo (LS mean difference [95% CI]=0.72 [0.29, 1.16]; p=0.001). Baseline mean FOSQ-10 total scores were 11.1 (3.1) for AXS-12 and 11.6 (3.2) for placebo. At Week 5, AXS-12 significantly improved FOSQ-10 score versus placebo (LS mean difference [95% CI]=1.66 [0.51, 2.82]; p=0.005). At baseline, 47.8% of participants in the AXS-12 arm and 45.5% in the placebo arm reported anxiety/depression (EQ-5D-5L); numerically more participants improved ≥1 level with AXS-12 (55.0%) versus placebo (31.6%) at Week 5 (p=0.146).
Conclusions
AXS-12 demonstrated a reduction in clinical impression of overall narcolepsy symptom severity, functional impairment due to EDS, and improved mood-related symptoms. Combined with prior findings, these results highlight the potential of AXS-12 to address narcolepsy symptoms affecting quality of life and functioning.
Short Description: AXS-12 (reboxetine) is a selective norepinephrine reuptake inhibitor and cortical dopamine modulator under investigation for narcolepsy. In the Phase 3 SYMPHONY study, AXS-12 significantly reduced cataplexy frequency. Here we report results from secondary endpoints, which show AXS-12 reduced the clinical impression of overall narcolepsy symptom severity, functional impairment due to excessive daytime sleepiness, and improved mood-related symptoms. These results highlight the potential for AXS-12 to address narcolepsy symptoms affecting quality of life and function.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc.
