Craig Chepke, MD: Excel Psychiatric Associates, Huntersville, NC, and Atrium Health, Charlotte, NC; Andrew J. Cutler, MD: SUNY Upstate Medical University, and Neuroscience Education Institute, Syracuse, NY; Samantha Floam, DMD: Axsome Therapeutics, New York, NY; Gregory, Parks, PhD: Axsome Therapeutics, New York, NY; Russell Rosenberg, PhD: Neurotrials Research, Atlanta, GA

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 (75-150 mg/day) or obstructive sleep apnea (OSA) (37.5-150 mg/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.

Post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or obstructive sleep apnea (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events.

On the maintenance of wakefulness test (MWT), 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, respectively. On the Epworth sleepiness scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg doses 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 (CGIc) as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in at least 5% of patients and greater than placebo were all >10, with the exception for headache in TONES 2 (NNH=6).

This post-hoc analysis demonstrates favorable effect size, NNT and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA.

Axsome Therapeutics