Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm

This work was sponsored by Axsome Therapeutics Introduction: Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor approved for treating excessive daytime sleepiness (EDS) in adults with narcolepsy or obstructive sleep apnea (OSA). This analysis characterizes effect size, number needed to treat (NNT), and number needed to harm (NNH) from two phase 3 studies (TONES 2 and TONES 3). Methods: We performed a post-hoc analysis of TONES 2 and TONES 3 data, studies focusing on EDS in adults with narcolepsy and OSA respectively. Effect size versus placebo, NNT, and NNH were calculated from established endpoints, post-hoc analyses, and adverse events. Results: Effect size (Cohen's d) on the maintenance of wakefulness test (MWT) ranged from 0.29 to 1.13 in TONES 2, and 0.46 to 1.28 in TONES 3. On the Epworth sleepiness scale (ESS), d ranged from 0.47 to 1.02 in TONES 2, and 0.37 to 1.04 in TONES 3. NNT for patients achieving an ESS ≤10 was 3-7 in TONES 2, and 3-8 in TONES 3. In patient global impression of change (PGIc), NNT was 3-4 in TONES 2 and 3-16 in TONES 3. Clinician global impression of change (CGIc) yielded similar NNT. For most adverse events with an incidence >5% and higher than placebo, NNH were >10, except for headache in TONES 2 (NNH=6). Conclusion: The post-hoc analysis supports solriamfetol's favorable effect size, NNT, and NNH for treating EDS associated with narcolepsy and OSA.