0740 Solriamfetol for Excessive Daytime Sleepiness in Narcolepsy and OSA: Post-hoc Multi-dimensional Composite Endpoint Analysis of Phase 3 Trials

Abstract Introduction Solriamfetol (Sunosi®) is a dopamine-norepinephrine reuptake inhibitor with agonist activity at the TAAR1 and serotonin 1A receptors approved for the treatment of EDS in narcolepsy (75-150 mg/day) or OSA (37.5-150 mg/day) in adults. To provide a more comprehensive understanding of treatment effect across objective and subjective outcomes, we evaluated clinically meaningful change in a composite assessment of primary and secondary endpoints from the Phase 3 TONES 2 (narcolepsy) and TONES 3 (OSA) trials. Methods TONES 2 and TONES 3 were double-blind, randomized, placebo-controlled, 12-week trials evaluating the safety/efficacy of solriamfetol for the treatment of EDS in narcolepsy or OSA, respectively. In both, co-primary efficacy endpoints were the change from baseline to week 12 in the MWT and ESS. The key secondary endpoint in both trials was the percentage of participants reporting improvement on the PGI-C at week 12. Clinically meaningful change was defined as ≥2 points reduction for ESS, ≥2 minutes increase for MWT, and minimal/much/very much improved for PGI-C. Results A total of 231 (TONES 2) and 459 (TONES 3) participants were included in the modified intent-to-treat populations. In TONES 2, the percentage of participants with composite clinically meaningful change in the co-primary and key secondary endpoints was 33.3% (absolute risk difference [95% CI]: 19.9% [3.6%, 36.1%]; P=0.018) in the solriamfetol 75 mg and 42.0% (absolute risk difference [95% CI]: 28.5% [12.0%, 45.1%]; P=0.001) in the solriamfetol 150 mg groups, compared with 13.5% in the placebo group. In the TONES 3 trial, the percentage of participants with composite clinically meaningful change in the co-primary and key secondary endpoints was 24.5% (absolute risk difference [95% CI]: 4.3% [-10.1%, 18.7%]; P=0.551) in the solriamfetol 37.5 mg, 40.7% (absolute risk difference [95% CI]: 20.5% [5.2%, 35.9%]; P=0.007) in the solriamfetol 75 mg, and 70.8% (absolute risk difference [95% CI]: 50.6% [38.8%, 62.3%]; P< 0.001) in the solriamfetol 150 mg groups, compared with 20.2% in the placebo group. Conclusion Treatment with 75 mg or 150 mg solriamfetol produced concurrent clinically meaningful, multi-dimensional change on objective and subjective measures of wakefulness, illustrating a comprehensive efficacy profile in patients with narcolepsy and OSA. Support (if any) Axsome Therapeutics Inc.