0560 Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm

Abstract

Abstract Introduction Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor that has been shown to activate TAAR1, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150mg/day) or obstructive sleep apnea (OSA) (37.5-150mg/day). Effect size, number needed to treat (NNT) and number needed to harm (NNH) are statistical representations of efficacy and tolerability that clinicians may find helpful in guiding treatment decisions. This analysis characterized these statistical parameters from two registrational studies. Methods We conducted a post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or OSA (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events. Results On the Maintenance of Wakefulness Test, effect size compared to placebo (Cohen’s d) was 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg doses of solriamfetol in TONES 2 and 0.46, 0.89, 1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg in TONES 3. On the Epworth Sleepiness Scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg in TONES 2, and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. NNT for patients achieving an ESS ≤10 was 7, 5, and 3 for 75mg, 150mg, and 300mg doses in TONES 2 and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. On the Patient Global Impression of Change (PGIc), NNT was 4, 3, and 3 for 75mg,150mg, and 300mg doses in TONES 2 and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg in TONES 3. Similar NNT were found for the Clinician Global Impression of Change as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in ≥5% of patients and greater than placebo were all >10, with the exception of headache in TONES 2 (NNH=6). Conclusion This post-hoc analysis demonstrates favorable effect size, NNT, and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA. Support (if any) Axsome Therapeutics