Solriamfetol (Sunosi)

Mechanism of action

Selective dopamine and norepinephrine reuptake inhibitor (DNRI) with additional agonist activity at trace amine-associated receptor 1 (TAAR1). Inhibits dopamine and norepinephrine reuptake with IC50 values of ~2.9 uM and ~4.4 uM (binding Ki ~14.2 uM at DAT and ~3.7 uM at NET); negligible serotonin transporter activity (Ki ~81.5 uM). Acts as a human/rodent TAAR1 agonist (EC50 ~10-16 uM) at concentrations overlapping its transporter activity -- a mechanism not shared by modafinil or bupropion -- and is a weak 5-HT1A agonist. The combined monoaminergic/TAAR1 profile is hypothesized to drive wake-promotion and is being tested for antidepressant and pro-vigilance effects in MDD with excessive daytime sleepiness.

Formulations

Solriamfetol (Sunosi) for Major depressive disorder

Phase 3RecruitingMajor depressive disorder indication →

Axsome's MDD development of solriamfetol. The broad Phase 3 proof-of-concept PARADIGM trial (NCT06360419; n=346; 300 mg once daily) did NOT meet its primary MADRS endpoint in the overall MDD population (topline 1 Apr 2025), but the prespecified subgroup of patients with severe excessive daytime sleepiness (EDS; ESS >=16, n=51) showed clinically meaningful, numerically greater improvements vs placebo across MADRS and global measures. Axsome therefore narrowed the program to MDD-with-EDS and initiated the Phase 3 CLARITY randomized-withdrawal trial (NCT07484217; 150 mg; primary endpoint time-to-relapse), first patient dosed late February 2026 (recruiting). Solriamfetol remains approved as Sunosi for EDS in narcolepsy/OSA (a separate indication).

Solriamfetol (Sunosi) for Attention-deficit/hyperactivity disorder

Phase 3ActiveAttention-deficit/hyperactivity disorder indication →

Axsome's development of solriamfetol for attention-deficit/hyperactivity disorder (ADHD) in adults. The pivotal Phase 3 FOCUS trial (NCT05972044; n=516 adults; solriamfetol 150 mg, 300 mg, or placebo once daily x6 weeks) MET its primary endpoint: the 150 mg dose produced a statistically significant reduction in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score vs placebo at Week 6 (-17.7 vs -14.3 points, p=0.039; ~45% mean improvement), with separation as early as Week 1 (p=0.036) and significant key secondary results (CGI-S p=0.017; AISRS response rate 53.5% vs 41.3%, p=0.024); the 300 mg dose was numerically superior but not statistically significant on the primary endpoint (topline 25 Mar 2025). An earlier MGH-sponsored investigator-initiated pilot (NCT04839562) was also positive. As of the Q4/FY2025 update (23 Feb 2026), Axsome has not disclosed an adult-ADHD sNDA submission and plans two pediatric Phase 3 trials (children and adolescents) to initiate in 1H 2026 following an FDA Type B meeting. Solriamfetol is separately approved as Sunosi for excessive daytime sleepiness in narcolepsy/OSA.

Solriamfetol (Sunosi) for Binge eating disorder

Phase 3RecruitingBinge eating disorder indication →

Axsome Therapeutics' development of solriamfetol for binge eating disorder (BED). The lead trial is the Phase 3 ENGAGE study (NCT06413433), a randomized, double-blind, placebo-controlled, multicenter trial in which approximately 450 adults with BED are randomized 1:1:1 to solriamfetol 150 mg, solriamfetol 300 mg, or placebo once daily for 12 weeks; the primary endpoint is the change from baseline to Week 12 in the number of binge eating episodes. The first patient was screened in March 2024; CT.gov status is recruiting. Axsome guides topline ENGAGE results to the second half of 2026. A separate open-label, long-term safety and efficacy study (NCT06878976; up to 52 weeks; solriamfetol 75/150/300 mg) supports the program. The mechanistic rationale is solriamfetol's dopamine/norepinephrine reuptake inhibition plus TAAR1 agonism. Solriamfetol remains approved as Sunosi for excessive daytime sleepiness in narcolepsy/OSA (a separate indication); it is not FDA-approved for BED.

Solriamfetol (Sunosi) for Excessive daytime sleepiness

Phase 3RecruitingExcessive daytime sleepiness indication →

Axsome Therapeutics' investigational development of solriamfetol for excessive sleepiness associated with shift work disorder (SWD). The pivotal Phase 3 SUSTAIN trial (NCT06568367) -- a multicenter, randomized, double-blind, placebo-controlled, parallel-group study -- evaluates solriamfetol 150 mg and 300 mg once daily vs placebo over 12 weeks in adults with excessive sleepiness due to SWD, with co-primary endpoints of change from baseline to Week 12 in Maintenance of Wakefulness Test (MWT) mean sleep latency and in Clinician Global Impression of Severity (CGI-S) for sleepiness during the night shift. SUSTAIN was initiated in 2024 (announced in Axsome's August 5, 2024 Q2 business update) and is recruiting (CT.gov actual start August 2024; estimated primary completion December 2026). Per Axsome's February 23, 2026 business update, topline results are now anticipated in 2027 based on current enrollment trends (revised from the earlier 2026 expectation). Solriamfetol is separately approved as Sunosi for EDS in narcolepsy and obstructive sleep apnea; SWD is not an approved indication.

Clinical trials