JZP-110 · program

Solriamfetol (Sunosi) for Attention-deficit/hyperactivity disorder

Phase 3ActiveAxsome Therapeutics, Inc. (AXSM)

Indications for JZP-110: Binge eating disorder · Phase 3 Excessive daytime sleepiness · Phase 3 Major depressive disorder · Phase 3 Attention-deficit/hyperactivity disorder · Phase 3

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.

Data current as of

Development timeline

Phase 3Jul 2023 – Mar 2025
  1. metFOCUS Phase 3 of solriamfetol in adult ADHD met its primary AISRS endpoint and key secondary endpoints (150 mg).↗
  2. Axsome initiated the registrational Phase 3 FOCUS trial of solriamfetol (150 mg and 300 mg) in adults with ADHD (NCT05972044); primary endpoint AISRS total score change at Week 6.
Phase 2/3Jan 2023
  1. Investigator-initiated MGH pilot (NCT04839562; Phase 2/3; n=60 dosed) of solriamfetol in adult ADHD reached primary completion; the study was positive (statistically significant ADHD symptom improvement vs placebo, p=0.0106), supporting further development.

Readouts

  • 2025-03-25ReportedTopline datametNCT05972044

    FOCUS Phase 3 of solriamfetol in adult ADHD met its primary AISRS endpoint and key secondary endpoints (150 mg). ↗

Clinical trials in Attention-deficit/hyperactivity disorder

NCT05972044FOCUSPhase 3Completedn=516

A Phase 3, Randomized, Double-blind, Placebo-controlled Trial of Solriamfetol in Adults With ADHD (FOCUS)

Started Jul 2023· Primary completion Feb 2025· 📍 42 sites across 1 country (United States)

metprimaryChange from baseline to Week 6 in AISRS total score (solriamfetol 150 mg vs placebo) (0.039)

Solriamfetol 150 mg once daily met the primary endpoint: AISRS total score decreased 17.7 points from baseline vs 14.3 points for placebo at Week 6 (p=0.039; ~45% mean symptom improvement). Separation from placebo seen as early as Week 1 (p=0.036). The 300 mg dose was numerically superior to placebo but did not reach statistical significance on the primary endpoint. effect_size (between-group LS-mean difference) not separately disclosed in the topline PR.

metsecondaryChange from baseline in CGI-S at Week 6 (solriamfetol 150 mg vs placebo) (0.017)

Key secondary endpoint met: solriamfetol 150 mg produced a statistically significant reduction in overall ADHD disease severity (CGI-S) vs placebo at Week 6 (p=0.017).

metsecondaryAISRS clinical response rate (>=30% reduction) at Week 6 (solriamfetol 150 mg vs placebo) (0.024)

Statistically significant responder rate: 53.5% of solriamfetol 150 mg patients achieved >=30% AISRS improvement vs 41.3% for placebo (p=0.024).

NCT04839562Phase 2/3Completedn=60

Solriamfetol for ADHD in Adults: A Double-Blind Placebo Controlled Pilot Study

Started Aug 2021· Primary completion Jan 2023· 📍 1 site across 1 country (United States)

metprimaryChange in ADHD symptoms (clinician-rated) vs placebo (0.0106)

Investigator-initiated MGH pilot (n=60 dosed): solriamfetol produced a statistically significant improvement in ADHD symptoms vs placebo on the primary outcome (p=0.0106); 13 solriamfetol participants achieved clinical improvement vs 2 on placebo (p=0.002). Results posted on ClinicalTrials.gov 4 Mar 2024.

Formulations

FormulationRouteRegimenPharmacokinetics
Solriamfetol oral tablet (Sunosi)
Film-coated tablets; administer once daily upon awakening. In excessive daytime sleepiness (narcolepsy/OSA), recommended dose 75-150 mg/day; initiate at 75 mg (OSA) or 37.5 mg (narcolepsy) and titrate; max 150 mg/day. Avoid administration within 9 hours of planned bedtime.
OralOnce dailyt½ 7.1 h · Tmax 2 h · F 95%

Mechanism of action (compound-wide)

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.

TargetActionAffinity
NETprimarySLC6A2Reuptake inhibitorKi 3700 nMⓘ
DATSLC6A3Reuptake inhibitorKi 14200 nMⓘ
TAAR1TAAR1Agonist—ⓘ

← Full JZP-110 compound page (identity, identifiers, all indications)

Sources

  1. Axsome Therapeutics Announces FOCUS Phase 3 Trial of Solriamfetol in Adults with Attention Deficit Hyperactivity Disorder (ADHD) Achieves Primary Endpoint — Axsome Therapeutics (GlobeNewswire)
  2. Baladi et al. Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol Exp Ther 2018;366(2):367-376 (PMID 29891587; DOI 10.1124/jpet.118.248120) — Journal of Pharmacology and Experimental Therapeutics (PubMed)
  3. FOCUS: A Phase 3, Randomized, Double-blind, Placebo-controlled Trial of Solriamfetol in Adults With ADHD (NCT05972044) — ClinicalTrials.gov
  4. Solriamfetol for ADHD in Adults: A Double-Blind Placebo Controlled Pilot Study (NCT04839562) — ClinicalTrials.gov (Massachusetts General Hospital)
  5. SUNOSI (solriamfetol) tablets, for oral use, CIV — Full Prescribing Information — FDA / DailyMed (NLM)