Axsome Therapeutics, Inc. · NASDAQ:AXSM
Axsome Therapeutics — Investor Day (December 2023)
95 slides from Axsome Therapeutics's investor day presentation, Dec 7, 2023
Slide 1: Solriamfetol Investor Day December 7, 2023
Solriamfetol Investor Day December 7, 2023
Slide 2: Forward-looking statements
Certain information contained in this presentation may include “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “pl
Slide 3: Today's KOL Speakers
Today’s KOL Speakers Andrew J. Cutler, MD Clinical Associate Professor of Psychiatry SUNY Upstate Medical University Susan McElroy, MD Chief Research Officer and Director of Psychopharmacology Research at the Lindner Center of HOPE at the University of Cincinnati Richard Bogan, MD Associate Clinical
Slide 4: Today's Agenda
Today’s Agenda Welcome Solriamfetol Overview TAAR1 MOA And Major Depressive Disorder (MDD) Attention Deficit Hyperactivity Disorder (ADHD) Q+A on TAAR1, MDD and ADHD Binge Eating Disorder (BED) Cognition Shift Work Disorder (SWD) Q+A on Cognition, BED, SWD Closing Remarks Mark Jacobson, COO Dr. Herr
Slide 5: Solriamfetol Overview
Solriamfetol Overview Herriot Tabuteau, MD
Slide 6: Rapidly Growing, CNS-Focused Biopharma
Rapidly Growing, CNS-Focused Biopharma 2 Marketed Products 9 New Target Indications 5 Late-stage Product Candidates 183 Potential Patients Targeted Million
Slide 7: Solriamfetol Pharmacology
Solriamfetol Pharmacology Dopamine Reuptake Inhibitor Norepinephrine Reuptake Inhibitor TAAR1 agonist 5-HT1A agonist Ki = 3.7 µM Ki = 14.2 µM EC50 = 10-16 µM EC50 = 25 µM solriamfetol
Slide 8: Applications of Solriamfetol Pharmacology
Applications of Solriamfetol Pharmacology Relevant Target Indication Wake Promoting Pro-Cognitive Antidepressant-like Weight and Appetite EDS in narcolepsy; OSA; ES in SWD ADHD, cognitive impairment in OSA, narcolepsy, MDD MDD, Anxiety Binge eating disorder ADHD: attention deficit hyperactivity diso
Slide 9: Unlocking the Clinical and Commercial Potential of Solriamfetol
Unlocking the Clinical and Commercial Potential of Solriamfetol Elucidate the pharmacology Correlate the pharmacology to mechanisms of disease Generate clinical proof of concept (pilot studies) Leverage existing clinical experience (observations relevant to potential new indications) Approach 1 2 3
Slide 10: Solriamfetol Target Indications
Phase 1 Phase 2 Phase 3 NDA Marketed Solriamfetol Target Indications Abbreviations: TAAR1 = Trace amine-associated receptor 1 Please see full Prescribing Information for Sunosi at www.Sunosi.com. Phase 1 Phase 2 Phase 3 NDA Attention Deficit Hyperactivity Disorder (ADHD) Solriamfetol for ADHD, BED,
Slide 11: Unlocking Solriamfetol Franchise Value
Unlocking Solriamfetol Franchise Value U.S./EU approval for treatment of EDS in OSA and narcolepsy Potential patient populations >22 million Near-Term Clinical Milestones ADHD MDD BED SWD Phase 3 trial readout 2H 2024 Phase 3 trial initiation 1Q 2024 Phase 3 trial initiation 1Q 2024 Phase 3 trial in
Slide 12: Trace Amine Associated Receptor Signaling and Psychiatric Disorders
Craig Chepke, MD, DFAPA Adjunct Associate Professor of Psychiatry, Atrium Health Medical Director, Excel Psychiatric Associates Trace Amine Associated Receptor Signaling and Psychiatric Disorders
Slide 13: Solriamfetol
Solriamfetol Solriamfetol initially developed as a dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI) with wake-promoting effects 1. H. Gursahani et al., CNS Spectr., vol. 28, no. 2, pp. 222–222, Apr. 2023 2. placeholder Solriamfetol 2019 U.S. FDA and 2020 EMEA approval to improve wak
Slide 14: What is TAAR1?
What is TAAR1? Trace amines (TAs) are structurally related to monoamine neurotransmitters, but found at much lower concentrations in the brain The existence of trace amines has been known for a century, but they were thought to be incidental metabolites of monoamines Gainetdinov RR, et al. Pharmacol
Slide 15: TAAR1: Adaptive Modulation of Neurotransmitters
TAAR1: Adaptive Modulation of Neurotransmitters TAAR1 is expressed both pre- and post-synaptically. Expression primarily intracellular but can be on cell membrane Adaptively modulates activity of several major neurotransmitter systems: TAAR1 modulates dopamine tone in the brain Dimerizes with D2 rec
Slide 16: TAAR1 is Expressed in Brain Regions Important to Neuropsychiatric Disorders
TAAR1 is Expressed in Brain Regions Important to Neuropsychiatric Disorders TAAR1 is expressed in areas of the brain relevant to neuropsychiatric disorders: Ventral tegmental area (VTA) Substantia nigra pars compacta (SNpc) Dorsal raphe Prefrontal cortex (PFC) Limbic areas: Amygdala Hippocampus Hypo
Slide 17: TAAR1 Agonists Have Wide-Ranging Effects in Preclinical Models
TAAR1 Agonists Have Wide-Ranging Effects in Preclinical Models Revel FG, et al. Mol Psychiatry. 2013;18(5):543-556. Rutigliano G, et al. Cell Mol Neurobiol. 2020;40(2):239-255. Dedic N, et al. J Pharm Exp Ther. 2019;371:1-14. Dedic N, et al. J Pharm Exp Ther. 2019;371(Suppl):1-38. Antidepressant Pro
Slide 18: 5-HT1A in the Brain
5-HT1A in the Brain Serotonin receptor 5-HT1A is widely distributed in the CNS in areas including the cerebral cortex, hippocampus, amygdala, and raphe nucleus 1 5-HT1A modulates several major neurotransmitter systems including norepinephrine, serotonin (5HT), dopamine2 5-HT1A activation may modulat
Slide 19: TAAR1 agonists in clinical development
TAAR1 agonists in clinical development Solriamfetol (Axsome): DNRI with TAAR1 and 5-HT1A agonist activity Only commercially-available TAAR1 agonist (for treatment of excessive daytime sleepiness in obstructive sleep apnea or narcolepsy) Ralmitaront (Roche): TAAR1 partial agonist Evaluated in two Pha
Slide 20: Solriamfetol activates TAAR1 and 5-HT1A
Solriamfetol activates TAAR1 and 5-HT1A Drug hTAAR1 EC50 µM (Emax) 5-HT1A IC50 µM hDAT IC50 µM hNET IC50 µM Solriamfetol 10-16 (100%) 25 3.21 14.4 Modafinil No dose response* Unknown 2.8 >100 Bupropion No dose response* No functional activity 0.26 2.79 5HT1A: serotonin 1A receptor; EC50: half maxima
Slide 21: Solriamfetol inhibits VTA neuron firing similar to known TAAR1 agonist
Solriamfetol inhibits VTA neuron firing similar to known TAAR1 agonist Solriamfetol inhibited firing by VTA neurons in a dose-dependent manner, similar to TAAR1 agonist RO5256390 Gursahani et al. Presented at Psych Congress 2022
Slide 22: Solriamfetol activates TAAR1 and 5-HT1A at clinically relevant concentrations
Solriamfetol activates TAAR1 and 5-HT1A at clinically relevant concentrations DAT: dopamine transporter ; NET: norepinephrine transporter D. Gozal et al. Presented at Psych Congress 2023 2. Gursahani et al. Presented at Psych Congress 2022 0 0 10-8 10-7 10-5 10-4 10-3 20 40 60 80 100 120 0 20 40 60
Slide 23: TAAR1 / 5-HT1A agonists may have applications in psychiatric and neurological disorders
TAAR1 / 5-HT1A agonists may have applications in psychiatric and neurological disorders Schizophrenia Generalized Anxiety Disorder Parkinson’s Disease Psychosis Shift Work Disorder EDS due to OSA or Narcolepsy Binge Eating Disorder ADHD Major Depressive Disorder Schizophrenia Generalized Anxiety Dis
Slide 24: Major Depressive Disorder (MDD)
Craig Chepke, MD, DFAPA Adjunct Associate Professor of Psychiatry, Atrium Health Medical Director, Excel Psychiatric Associates Major Depressive Disorder (MDD)
Slide 25: MDD Is a Highly Prevalent and Heterogenous Disorder
Major Depressive Disorder (MDD) Is a Highly Prevalent and Heterogenous Disorder1-3 DSM-5-TR, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. *According to a study of 36,309 adult participants surveyed in the 2012-2013 National Epidemiologic Survey on Alcohol and
Slide 26: Remission Rates Decreased and Discontinuations Increased with Each Change in STAR*D
Remission Rates Decreased and Discontinuations Due to Side Effects Increased with Each Change in STAR*D Rates of remission and discontinuation due to intolerable side effects Each step of therapy included options to switch or augment, including various SSRIs, SNRIs, lithium, T3, TCAs, MAOIs, combina
Slide 27: TAAR1 Agonists Show Preclinical Evidence of Potential Benefits in MDD
TAAR1 Agonists Show Preclinical Evidence of Potential Benefits in MDD The combination of a monoamine reuptake inhibitor and TAAR1/5-HT1A agonist showed synergistic results in two mouse models of MDD which often reliably predict antidepressant efficacy FST=forced swimming test; TST= tail suspension t
Slide 28: Hypothesized MOA of TAAR1 Agonists in MDD
Hypothesized MOA of TAAR1 Agonists in MDD Involves Multiple Intracellular Signal Transduction Cascades References: adapted from Alnefeesi, Yazen, et al. "Trace amine-associated receptor 1 (TAAR1): Potential application in mood disorders: A systematic review." Neuroscience & Biobehavioral Reviews 131
Slide 29: High Level Summary of TAAR1 MOA in MDD
High Level Summary of TAAR1 MOA in MDD References: Alnefeesi, Yazen, et al. "Trace amine-associated receptor 1 (TAAR1): Potential application in mood disorders: A systematic review." Neuroscience & Biobehavioral Reviews 131 (2021): 192-210.
Slide 30: MDD: Axsome Planned Phase 3 Trial
Major Depressive Disorder (MDD): Axsome Planned Phase 3 Trial Key Inclusion Criteria: Meets DSM-5 criteria for MDD MADRS score of ≥25 and a CGI-S ≥4 at screening and baseline Primary Endpoint: Safety measures including AEs, TEAEs, ECG readings and C-SSRS AXS-05 twice daily Placebo Double-blind Phase
Slide 31: Key Takeaways for TAAR1 MOA in MDD
Key Takeaways for TAAR1 MOA in MDD TAAR1 and 5-HT1A agonists as compelling drug development target in neuropsychiatry Agents with TAAR1 and 5-HT1A agonist activity have shown potential in neuropsychiatry Solriamfetol, the only commercially available TAAR1 agonist, has potential in multiple new targe
Slide 32: Overview of Attention Deficit Hyperactivity Disorder (ADHD)
Andrew Cutler, MD SUNY Upstate Medical University and Neuroscience Education Institute, Syracuse, NY Overview of Attention Deficit Hyperactivity Disorder (ADHD)
Slide 33: What is ADHD?
What is ADHD? The presence of developmentally inappropriate levels of hyperactive-impulsive and/or inattentive symptoms for at least 6 months. Six or more symptoms in one or both domains required for youth Five or more for adults Symptoms occur in different settings (e.g., home and school). Some sym
Slide 34: ADHD is a Common Disorder in Childhood and Adulthood
ADHD is a Common Disorder in Childhood and Adulthood An estimated 17.4 million people in the U.S. are affected by ADHD1,2 The prevalence of ADHD has not changed over the past three decades that have data available3 No significant differences in prevalence between North America and Europe, Asia, Afri
Slide 35: Neural basis of ADHD
Neural basis of ADHD Neurotransmitter Pathways Implicated in ADHD1 Fronto-striatal and fronto-parietal networks in ADHD Under-activation of fronto-striatal and fronto-parietal networks consistent with impaired goal-directed executive processes Under-activation of frontal control over the limbic syst
Slide 36: Current Treatments and Unmet Need
Current Treatments and Unmet Need FDA-Approved Stimulants Methylphenidate and Amphetamine IR and ER formulations Duration range 4 to 16 hours Liquid and chewable forms available FDA-Approved Non-Stimulants Atomoxetine (NET reuptake inhibitor) Viloxazine ER (NET reuptake inhibitor; binds to 5-HT2A, 5
Slide 37: Current Treatments and Unmet Need
Current Treatments and Unmet Need Stimulants Schedule II controlled substances Misuse, abuse and diversion risk Irritability/rebound phenomena; Loss of ‘sparkle’ Non-Stimulants Low effect sizes for all Clonidine and guanfacine: sedation, lack of data in adults with ADHD Atomoxetine: black box for su
Slide 38: Solriamfetol for ADHD in Adults: Pilot Study Design
Solriamfetol for ADHD in Adults: A Double-Blind Placebo-Controlled Pilot Study 1. Surman, C. B. H. et al. Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study. J. Clin Psychiatry 2023;84(0):23m14934 Trial Design: 6 week randomized double-
Slide 39: Solriamfetol for ADHD in Adults: Demographic and Baseline Characteristics
Solriamfetol for ADHD in Adults: Demographic and Baseline Characteristics 1. Adapted from: Surman, C. B. H. et al. Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study. J. Clin Psychiatry 2023;84(0):23m14934 Abbreviations: CGI = Clinical
Slide 40: Solriamfetol for ADHD in Adults: AISRS Results
Solriamfetol for ADHD in Adults: A Double-Blind Placebo-Controlled Pilot Study For Weeks 3-6, mean improvement in total AISRS ratings was significantly greater for solriamfetol-treated individuals than for placebo-treated The mean total improvement in AISRS score by Week 6 was –7.6 for active study
Slide 41: Solriamfetol for ADHD in Adults: CGI Results
Solriamfetol for ADHD in Adults: A Double-Blind Placebo-Controlled Pilot Study By week 6, CGI ratings of much or very much improved occurred for significantly more individuals on solriamfetol (45%, 13/29) than placebo (6%, 2/31) (P = .0020). Solriamfetol treatment: much improved: 24% (7 individuals)
Slide 42: Solriamfetol for ADHD in Adults: Safety and Tolerability
Solriamfetol for ADHD in Adults: Safety and Tolerability Safety and tolerability of solriamfetol was in line with previous clinical studies
Slide 43: Solriamfetol Pilot ADHD Trial Conclusions
Solriamfetol Pilot ADHD Trial Conclusions In this single-center pilot trial conducted at Massachusetts General Hospital in Boston, solriamfetol was associated with significantly greater improvement in ADHD symptoms compared to placebo on the AISRS (primary endpoint). Results on secondary endpoints i
Slide 44: ADHD: Axsome FOCUS Phase 3 Trial
Attention Deficit Hyperactivity Disorder: Axsome FOCUS Phase 3 Trial Primary Endpoint: Change in the Adult ADHD Investigator Symptom Report Scale (AISRS) Key Inclusion Criteria: Adults, aged 18 to 55 inclusive. Primary diagnosis of ADHD (inattentive, hyperactive, or combined subtype) using DSM-5 cri
Slide 45: Key Takeaways for Solriamfetol in ADHD
Key Takeaways for Solriamfetol in ADHD An estimated 17.4 million people in the U.S. are affected by ADHD and prevalence has not changed for the past three decades that have data available1,2 ADHD is associated with significant impairment in social, academic, and occupational functioning or developme
Slide 46: Q+A on TAAR1, MDD, and ADHD
on TAAR1, MDD, and ADHD Q+A Andrew J. Cutler, MD Craig Chepke, MD, DFAPA
Slide 47: Solriamfetol in Binge Eating Disorder
Susan L. McElroy, MD Chief Research Officer, Lindner Center of HOPE Linda & Harry Fath Professor of Psychiatry & Behavioral Neuroscience University of Cincinnati College of Medicine Cincinnati, Ohio Solriamfetol in Binge Eating Disorder
Slide 48: Disclosures
Disclosures 2023 Principal/Co-Investigator Allergan, Avanir, Brainsway, Marriott Foundation, Myriad, Neurocrine, Novo Nordisk, Shire, Sunovion Consultant/Ad Board Allergan, Avanir, Bracket, F. Hoffman-La Roche Ltd., Idorsia, Mitsubishi Tanabe, Myriad, Shire, Sunovian Patents Inventor on United State
Slide 49: Outline
Outline Brief overview of Binge Eating Disorder (BED) Brief overview of treatment of BED Overview for rationale of solriamfetol in BED
Slide 50: Definition of a Binge
Definition of a “Binge” Eating, in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances A sense of lack of control over eating during the episode (e.g., a fee
Slide 51: Binge Eating Disorder (BED)
Binge Eating Disorder (BED) Binge Eating: Eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances AND a sense of lack of control overeating Binge Eating Disorder: BED broadly defined as recurrent binge eating wit
Slide 52: DSM-5 Criteria for BED
DSM-5 Criteria for BED 1. APA. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 2013. * Denotes a change from DSM-IV criteria General Presentation Recurrent episodes of binge eating occurring at least once a week for 3 months* Eating a larger amount of food than normal during a
Slide 53: BED Epidemiology/Course
BED Epidemiology/Course BED is the most common eating disorder 2.8% (US adults), 1.6% (adolescents), 1.9% worldwide Prevalence for other eating disorders: Anorexia Nervosa 0.6%, Bulimia Nervosa 1% BED affects women(3.5%) more often than men (2.0%) BED is more common in men than other eating disorder
Slide 54: BED is Associated With…
BED is Associated With… Overeating (night eating, grazing, LOC) and weight gain Obesity, including severe obesity (BMI ≥40), & obesity-related conditions Mood, anxiety, substance use, impulse control (e.g., ADHD) disorders 80% have ≥1 comorbid disorder Reduced quality of life, impairment in function
Slide 55: Most People With BED Remain Untreated
Most People With BED Remain Untreated 12-Month Treatment for BED: 28.4% of those with disorder have received treatment Lifetime Treatment for BED: 43.6% of those with disorder have received treatment Hudson JI et al. Biol Psychiatry. 2007;61:348.
Slide 56: Standard of Care for BED not yet clearly defined
Standard of Care for BED not yet clearly defined Psychoeducation, self-help strategies Behavioral weight loss treatment Empirically based psychotherapies (ex.CBT-E) Pharmacotherapy Obesity surgery Combination therapy McElroy SL et al. Ther Clin Risk Manag. 2012;8:219.
Slide 57: Pharmacotherapy of BED
Pharmacotherapy of BED Only 1 drug with FDA approval for BED: Lisdexamfetamine for BED Fluoxetine for BN Dasotraline development for BED halted despite 2 positive RCTs Problems with lisdexamfetamine: Addiction (schedule 2) Cardiovascular side effects Can be mood destabilizing Not everyone responds o
Slide 58: Dasotraline
Dasotraline Selective DA-NE reuptake inhibitor Was being developed for ADHD and BED 2 positive registration trials for BED Navia B et al, 2017. APA 170th Meeting
Slide 59: Dasotraline in BED
Dasotraline in BED Change in binge-eating days per week in randomized, placebo-controlled, flexible-dose clinical trial: Navia B et al, 2017. APA 170th Meeting
Slide 60: Rationale for Solriamfetol in BED
Rationale for Solriamfetol in BED DNRI like dasotraline Decreased appetite and weight loss Link between narcolepsy and BED
Slide 61: Solriamfetol: Preclinical Effects on Food Intake
Solriamfetol: Preclinical Effects on Food Intake 1. Axsome Therapeutics, Inc., “Solriamfetol (previously JZP-110) [Investigator’s Brochure].” 2023. 2. Study No. JNJ-7006, non-GLP 3. Study No. 95-4a, non-GLP Administration of solriamfetol to mice and rats under a variety of conditions consistently re
Slide 62: Solriamfetol: Clinical Effects on Appetite and Weight
Solriamfetol: Clinical Effects on Appetite and Weight During 12-week randomized clinical trials for OSA and narcolepsy, decreased appetite was one of the most common adverse events with solriamfetol and occurred in a dose-dependent fashion Abbreviation: TEAE = treatment emergent adverse event; OSE =
Slide 63: Solriamfetol: Clinical Effects on Weight
Solriamfetol: Clinical Effects on Weight Percent of patients with ≥5% weight decrease during 40-week open-label clinical trials for OSA and narcolepsy: Abbreviation: TEAE = treatment emergent adverse event 1. Malhotra A et al. Sleep Med. 100(2022) pp 165-173. n= 374 n= 225 n= 127 n= 22 n= 124 n= 90
Slide 64: BED: Axsome Planned Phase 3 Trial
Binge Eating Disorder: Axsome Planned Phase 3 Trial Key Inclusion Criteria: Meets DSM-5 criteria for BED Diagnosis confirmed by EDE-Q Primary Endpoint: Change from baseline in the diary reported number of binge eating days per week Registrational Trial AXS-05 twice daily Solriamfetol (150 mg) Placeb
Slide 65: Key Takeaways for Solriamfetol in Binge Eating Disorder
Key Takeaways for Solriamfetol in Binge Eating Disorder BED is the most common eating disorder, affecting almost 3% of the U.S. population1 BED is associated with a 2- to 3-fold increased risk of psychiatric and medical comorbidities2 Despite high prevalence and burden, there is currently only one F
Slide 66: SHARP Study: Effects of Solriamfetol on Cognitive Function in OSA
Richard Bogan, M.D. Associate Clinical Professor at the University of South Carolina School of Medicine and Medical University of South Carolina Principal of Bogan Sleep Consultants SHARP Study: Effects of Solriamfetol on Cognitive Function in Participants With Cognitive Impairment Associated With E
Slide 67: Background
Background Excessive daytime sleepiness (EDS) is a common symptom of obstructive sleep apnea (OSA). It can persist in 10%–28% of patients, despite use of primary airway therapy Patients with EDS associated with OSA may have performance deficits in several cognitive domains Solriamfetol (Sunosi®) is
Slide 68: SHARP Trial Study Design
Baseline Visit 3 Double-Blind Treatment Period 1 Safety Follow-up Period Placebo 2-4 weeks Double-Blind Treatment Period 2 4-10 days after last dose Safety Visit 9 Screening Visit 1 Week 2 Visit 5 Week 5 Visit 8 2 weeks 1 week Solriamfetol 75 mg/day for 3 days, then 150 mg/day Screening Period Solri
Slide 69: Clinical Visit Structure
Arrive Depart Safety evaluation Confirm protocol compliance, weight, vitals Patient Global Impression of Severity (PGI-S) Epworth Sleepiness Scale (ESS) British Columbia Cognitive Complaints Inventory (BC-CCI) Coding Subtest (a variation of the Digit Symbol Substitution Test) of the Repeatable Batte
Slide 70: SHARP Participant Baseline Characteristics
Of 173 participants screened, 59 were enrolled, and 57 completed the study Among participants using positive airway pressure, average use was ≥6 hours per night Solriamfetol/ placebo (n=30) Placebo/ solriamfetol (n=29) Overall (N=59) Age (years), mean (SD) 52.5 (10.5) 51.9 (11.1) 52.2 (10.7) Sex (fe
Slide 71: Study Findings: Objective Cognitive Function
Improvement in cognitive function P=0.009 Solriamfetol significantly improved objective cognitive function compared with placebo Mean difference: 1.75 (95% CI: 0.46, 3.04) Cohen’s d: 0.36 Change from baseline to end of treatment in objective cognitive function was measured with the Coding Subtest (a
Slide 72: Study Findings: Objective Cognitive Function by Timepoint
Solriamfetol (n=58) Placebo (n=58) P=0.033 P=0.022 Solriamfetol significantly improved objective cognitive function compared with placebo at 2, 6, and 8 hours after dosing Mean difference (95% CI) 2-hour: 1.91 (0.16, 3.65) 4-hour: 1.38 (−0.22, 2.97) 6-hour: 2.33 (0.78, 3.88) 8-hour: 1.58 (0.23, 2.93
Slide 73: Study Findings: Subjective Cognitive Function
Solriamfetol significantly improved subjective cognitive function compared with placebo Mean difference: −1.58 (95% CI: −2.53, −0.63) Cohen’s d: 0.43 P=0.002 Improvement in cognitive function Change from baseline to end of treatment in subjective cognitive function was measured with the British Colu
Slide 74: Study Findings: Safety
All treatment-emergent adverse events (TEAEs) were mild or moderate in severity There were no deaths, serious TEAEs, or TEAEs that led to discontinuation of the study n (%) Solriamfetol (n=58) Placebo (n=58) Any TEAE 11 (19) 6 (10) Nausea 4 (7) 1 (2) Anxiety 2 (3) 0 Insomnia 1 (2) 1 (2) Nasopharyngi
Slide 75: Conclusions
Conclusions Solriamfetol provided sustained improvement in objective cognition, reduced participants’ perceived severity of cognitive impairment, and reduced subjective sleepiness The adverse event profile and high study completion rate suggest solriamfetol was well tolerated Solriamfetol has the po
Slide 76: Shift Work Disorder: Diagnostic Features, Prevalence, Adverse Health Outcomes, and Approved Treatments
Charles A. Czeisler, PhD, MD, FRCP, FAPS Frank Baldino, Jr, PhD Professor of Sleep Medicine Professor of Medicine and Director, Division of Sleep Medicine, Harvard Medical School Chief, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women’s Hospital Shift
Slide 77: Disclosures
Disclosures 1. Modafinil for Shift-Work Sleep-Wake Disorder1,3 2. Armodafinil for Shift-Work Sleep-Wake Disorder2 3. Tasimelteon for Non-24-Hour Sleep-Wake Disorder4,5 1. Czeisler CA et al. (2005). Modafinil for excessive sleepiness associated with shift work sleep disorder. N Engl J Med 353: 476-48
Slide 78: Shift Work Disorder: Diagnostic Features
Shift Work Disorder: Diagnostic Features Insomnia during daytime sleep or excessive sleepiness during night work, accompanied by reduced total sleep time Associated with work schedule that overlaps usual sleep time Symptoms cause clinically significant distress or impairment in important areas of fu
Slide 79: SWD Prevalence Studies
Study Prevalence estimate 2004 Drake CL et al. Shift work sleep disorder: prevalence and consequences…. Sleep Insomnia during day sleep OR excessive sleepiness during night work: 32% night workers; 26% rotating shift workers (vs 18% of day workers) 2009 Waage S et al. Shift work disorder among oil r
Slide 80: SWD Prevalence Studies
Study Prevalence estimate 2004 Drake CL et al. Shift work sleep disorder: prevalence and consequences…. Sleep Insomnia during day sleep OR excessive sleepiness during night work: 32% night workers; 26% rotating shift workers (vs 18% of day workers) 2009 Waage S et al. Shift work disorder among oil r
Slide 81: Genetic background matters
Night-shift workers carrying the five-repeat variant of the Period 3 gene (Period 3–/5), which make up about 35–40% of the population, showed elevated levels of nocturnal sleepiness and earlier circadian phase compared with homozygotes for the four-repeat allele (Period 34/4). Long-allele carrier sh
Slide 82: Study Outcomes
Study Outcomes 1999 Bøggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J Work Environ Health Night shift work associated with 40% increased risk of cardiovascular disease (not specific to Shift Work Disorder) 2004 Drake CL et al. Shift work sleep disorder: prevalence a
Slide 83: Management Strategy for Shift Work Disorder
Ref: Roth T. Appropriate therapeutic selection for patients with shift work disorder. Sleep Med. 2012 Apr;13(4):335-41. doi: 10.1016/j.sleep.2011.11.006. Epub 2012 Feb 20. PMID: 22353444. Management Strategy for Shift Work Disorder
Slide 84: Evidence for non-pharmacological interventions review
“Given the methodological diversity of the included studies, in terms of interventions, settings, and assessment tools, their limited reporting and the very low to low quality of the evidence they present, it is not possible to determine whether shift workers' sleepiness can be reduced or if their s
Slide 85: Only five randomized trials of wake-promoting therapeutics in SWD
Ref: Conway-Jones R, Dunlop E, Kyle S, Ray D, Roberts N, Farmer A. A scoping review of the evidence for the impact of pharmacological and non-pharmacological interventions on shift work related sleep disturbance in an occupational setting. Wellcome Open Res. 2023 Jan 6;6:198. doi: 10.12688/wellcomeo
Slide 86: FDA Registration Trial for ES associated with a CRSWD
FDA Registration Trial for ES associated with a CRSWD
Slide 87: Only Two Treatments are FDA-approved for Excessive Sleepiness Associated with SWD
Ref: Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, Arora S, Schwartz JR, Niebler GE, Dinges D. Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med. 2005 Aug 4;353(5):476-86. Ref: Czeisler CA, Walsh JK, Wesnes KA, Arora S, Roth T. Armodafinil
Slide 88: Shift Work Disorder is simple to identify by a primary care physician
“A final 4-item questionnaire has 89% positive predictive value and 62% negative predictive value (sensitivity = 0.74; specificity = 0.82).” Ref: Barger LK, Ogeil RP, Drake CL, O'Brien CS, Ng KT, Rajaratnam SM. Validation of a questionnaire to screen for shift work disorder. Sleep. 2012;35:1693-1703
Slide 89: Improvement in Objective Measure of Sleepiness in OSA
Ref: Schweitzer PK, Mayer G, Rosenberg R, Malhotra A, Zammit GK, Gotfried M, Chandler P, Baladi M, Strohl KP. Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment. Chest. 2021;160:307-318. Improvement i
Slide 90: Improvement in Subjective Measure of Sleepiness in OSA
Ref: Schweitzer PK, Mayer G, Rosenberg R, Malhotra A, Zammit GK, Gotfried M, Chandler P, Baladi M, Strohl KP. Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment. Chest. 2021;160:307-318. Improvement i
Slide 91: Improvement in Subjective Measure of Sleepiness in Narcolepsy
Ref: Thorpy MJ, Shapiro C, Mayer G, Corser BC, Emsellem H, Plazzi G, Chen D, Carter LP, Wang H, Lu Y, Black J, Dauvilliers Y. A randomized study of solriamfetol for excessive sleepiness in narcolepsy. Ann Neurol. 2019;85:359-370 Improvement in Subjective Measure of Sleepiness (measured using the Epw
Slide 92: Shift Work Disorder: Need for Treatment
Shift Work Disorder: Need for Treatment Shift work disorder affects about 12 million American workers Patients with shift work disorder are at increased risk of errors and accidents, including motor vehicle crashes, and adverse health outcomes Evidence for efficacy of commonly used non-pharmacologic
Slide 93: Q+A on Cognition and BED
on Cognition and BED Q+A Richard Bogan, MD Susan McElroy, MD
Slide 94: Closing Remarks
Closing Remarks Herriot Tabuteau, MD
Slide 95: Thank you
nasdaq: axsm thank you cxtome