Auvelity (bupropion/dextromethorphan) / Axsome Therap - LARVOL DELTA

New and emerging pharmacologic treatments for MDD. (PubMed, Front Psychiatry) - "Furthermore, the combination of dextromethorphan and bupropion has shown promise. Brexanolone, administered via infusion, and zuranolone, available as an oral formulation, both have demonstrated efficacy in clinical settings. Novel treatments targeting opioid pathways, such as esmethadone, and selective kappa receptor antagonists offer new hope for addressing the symptoms of MDD through mechanisms not traditionally associated with antidepressant action."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Axsome Therapeutics Hosts Frontiers in Brain Health R&D Day Reviewing Industry-Leading Late-Stage CNS Pipeline (GlobeNewswire) - "Dr. Chadwick will provide an overview of fibromyalgia and of the previously completed Phase 2 and Phase 3 clinical trials of AXS-14 in the indication...Dr. Cummings will provide an overview of Alzheimer's disease (AD) agitation and discuss the results of the ADVANCE and ACCORD Phase 3 trials of AXS-05 in the indication...Cutler will provide an overview of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) with excessive daytime sleepiness (EDS), and excessive sleepiness associated with shift work disorder (SWD), and discuss the results of the FOCUS and PARADIGM Phase 3 trials of solriamfetol in ADHD and MDD, respectively...Dr. Tepper will provide an overview of migraine and will discuss results from the MOMENTUM and INTERCEPT Phase 3 trials of SYMBRAVO in the acute treatment of migraine with and without aura....Dr. Thorpy will provide an overview of narcolepsy and will discuss the results of the clinical trial program of AXS-12 in the indication."

Clinical data • Trial status • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • Excessive Daytime Sleepiness • Fibromyalgia • Major Depressive Disorder • Migraine • Narcolepsy • Psychiatry • Sleep Disorder

All Roads Lead to Glutamate: NMDA and AMPA Receptors as Targets for Rapid-Acting Antidepressants. (PubMed, Pharmacol Res) - "Beyond established rapid-acting antidepressants (RAADs), such as (es)ketamine and dextromethorphan/bupropion (AXS-05), we highlight novel therapeutic directions involving esmethadone (REL-1017), nitrous oxide, and positive allosteric modulators (PAMs) of NMDA receptors (e.g. rapastinel, zelquistinel, and apimostinel). Moreover, we discuss forward-looking strategies using AMPA receptor PAMs (e.g. osavampator and tulrampator) and targeting of AMPA receptor-interacting proteins...Together, targeting glutamatergic signalling represents a transformative path for TRD treatment with high efficacy by more directly modulating pathologically affected signalling modules. These developments place glutamatergic agents at the forefront of next-generation AD strategies."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Real-world signal detection of adverse events associated with Auvelity(bupropion-dextromethorphan): A pharmacovigilance study based on the FAERS database. (PubMed, Asian J Psychiatr) - No abstract available

Adverse events • Journal • Real-world evidence • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: Virginia Commonwealth University | Recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Jul 2025 | Trial primary completion date: Jan 2026 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse

Commercial Highlights (GlobeNewswire) - "Payer coverage for AUVELITY in the commercial channel expanded by 28 million new covered lives as of July 1. Overall payer coverage for AUVELITY across all channels is now at approximately 83% of all lives covered, with the proportion of covered lives in the commercial and government (Medicare and Medicaid) channels at approximately 73% and 100%, respectively...Payer coverage for SUNOSI across all channels is at approximately 83% of all lives covered. The proportion of lives covered for SUNOSI in the commercial and government channels are approximately 95% and 60%, respectively...Effective July 1, Axsome has contracted with one of the three largest...(GPOs) for potential formulary coverage of SYMBRAVO....Payer coverage for SYMBRAVO across all channels is currently at approximately 38% of all lives covered. The proportion of lives covered in the commercial and government (Medicare and Medicaid) channels are currently approximately 26% and 56%, respectively."

Commercial • Major Depressive Disorder • Migraine • Narcolepsy • Obstructive Sleep Apnea

Anticipated Milestones (GlobeNewswire) - "Regulatory and Commercial: AXS-05 for Alzheimer’s disease agitation, sNDA submission (3Q 2025); AXS-12 for narcolepsy, NDA submission (4Q 2025)...Clinical Trial Initiations and Progress....Phase 3 trial of solriamfetol in ADHD in pediatric patients, initiation (4Q 2025); Phase 3 trial of solriamfetol in MDD with EDS, initiation (4Q 2025)."

FDA filing • New P2/3 trial • New P3 trial • Alzheimer's Disease • Excessive Daytime Sleepiness • Major Depressive Disorder • Narcolepsy

Axsome Therapeutics Reports Second Quarter 2025 Financial Results... (GlobeNewswire) - "AUVELITY net product sales were $119.6 million for the second quarter of 2025, representing 84% year-over-year growth, and 24% sequential growth compared to the first quarter of 2025. AUVELITY net product sales for the second quarter of 2024 were $65.0 million; SUNOSI net product revenue was $30.0 million for the second quarter of 2025, representing 35% year-over-year growth, and 19% sequential growth compared to the first quarter of 2025. SUNOSI net product revenue for the second quarter of 2025 consisted of $28.9 million in net product sales and $1.1 million in royalty revenue associated with SUNOSI sales in out-licensed territories....SYMBRAVO was launched on June 10, 2025, and had net product sales of $0.4 million for the second quarter of 2025. No SYMBRAVO sales were reported by Axsome for the comparable period in 2024 reflecting the timing of the product launch."

Sales • Major Depressive Disorder • Migraine • Narcolepsy • Obstructive Sleep Apnea

Efficacy and safety of dextromethorphan-bupropion combination (AXS-05) in the treatment of depression: A systematic review and network meta-analysis. (PubMed, Indian J Pharmacol) - "Despite a higher incidence of mild to moderate adverse events (72.9% vs. 64.6% for Bupropion), the combination's safety profile remained comparable, with no significant increase in treatment discontinuation. These results suggest that AXS-05 is a promising treatment for MDD, warranting further investigation in larger, diverse populations to confirm its long-term efficacy and safety."

Clinical • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Contrave, Lybalvi, Auvelity, and Cobenfy: What Do They Have in Common? (PubMed, J Psychiatr Pract) - "This column reviews 4 psychiatric combination products: Contrave (bupropion + naltrexone), Lybalvi (olanzapine + samidorphan), Auvelity (dextromethorphan + bupropion), and Cobenfy (xanomeline + trospium). In each case, the second drug in the combination enhances the efficacy and/or reduces the adverse effects of the first drug. This review illustrates how basic science in pharmacokinetics and brain circuitry was fundamental to the development of these products, particularly in the case of Contrave and Cobenfy."

Journal • Review • Psychiatry

Fixed dose combination dextromethorphan-bupropion: A hope for treatment resistant depression (TRD). (PubMed, Indian J Psychiatry) - "Olanzapine-fluoxetine combination, rTMS, Intravenous ketamine and Electroconvulsive therapy have been till now studied in TRD. Dextromethorphan-bupropion is a newer antidepressant, which has been found to be effective, fast-acting, and well tolerated medicine for depression. We used this novel antidepressant in three cases of TRD, alone and with combination, and it showed satisfactory response within 2 weeks."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Efficacy and Safety of AXS-05 in Alzheimer's Disease Agitation: A Phase 3 Randomized-Withdrawal Double-Blind Placebo-Controlled Study (ASCP 2025) - "AXS-05 achieved primary and key secondary endpoints by statistically significantly delaying and preventing AD agitation relapse versus placebo, respectively. AXS-05 prevented worsening of severity of AD agitation and AD overall compared to placebo. AXS-05 was well tolerated, with no new safety signals."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders

Deuteration may reduce the efficacy of dextromethorphan in treating agitation in Alzheimer's disease. (PubMed, Alzheimers Res Ther) - "Axsome Therapeutics has reported positive results in three out of four clinical trials evaluating AXS-05, a combination of dextromethorphan with another CYP2D6 inhibitor, bupropion. However, in our patch-clamp experiments, deuteration resulted in a 16-fold increase in IC50 for dextrorphan and about two-fold increase for dextromethorphan at NMDA receptors containing the NR2D subunit. Thus, based on both clinical data and emerging pharmacological evidence, we hypothesize that AVP-786 failed to demonstrate efficacy in treating agitation in AD dementia due to the negative impact of deuteration on dextromethorphan's pharmacodynamic properties."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry

Axsome Therapeutics Presents Data from Three of Its Innovative Neuroscience Programs at the American Society of Clinical Psychopharmacology (ASCP) 2025 Annual Meeting (GlobeNewswire) - "Axsome Therapeutics, Inc...announced presentations from three of its innovative neuroscience programs at the American Society of Clinical Psychopharmacology (ASCP) 2025 Annual Meeting, being held from May 27-30 in Scottsdale, Arizona."

Clinical data • Alzheimer's Disease • Depression • General Anxiety Disorder • Major Depressive Disorder • Narcolepsy

New Vistas in the Treatment of Mood and Anxiety Disorders: Psychedelics, Neuromodulation and More (APA 2025) - "The combination of dextromethorphan and bupropion was recently FDA approved for major depression, as was intranasal esketamine. Promising novel agents under scrutiny in clinical trials for depression include lumateperone, already approved for the treatment of schizophrenia and bipolar disorder, esmethadone, a non-mµ opiate receptor antagonist and more than one kappa opiate antagonist for the treatment of depression with prominent anhedonia, positive allosteric modulators of the GABA-A receptor for GAD and MDD (as a follow up to the approval of brexanolone and zuranolone for the treatment of post-partum depression), a novel agent that acts as a thyroid hormone receptor agonist for MDD, fasedienol for the treatment of social anxiety disorder, a novel intracellular modulator of MTORC1 in the treatment of depression, triple (DA, NE, 5HT) reuptake inhibitors for depression and an orexin antagonist for the treatment of depression. Instructional Level Intermediate;..."

Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Social Anxiety Disorder • Vascular Neurology

AXS-05-AD-305: An Open-Label Study to Assess the Long-term Safety of AXS-05 in Subjects With Dementia of the Alzheimer's Type, ADVANCE-2 and ACCORD-2 Extension Study (clinicaltrials.gov) - P3 | N=139 | Terminated | Sponsor: Axsome Therapeutics, Inc. | Trial completion date: Aug 2025 ➔ Apr 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Feb 2025; Study AXS-05-AD-305 was terminated due to completion of overall program objectives.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders • Dementia

Axsome Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Regulatory and Commercial: SYMBRAVO for the acute treatment of migraine, commercial launch (June 2025); AXS-14 for fibromyalgia, FDA filing acceptance decision (2Q 2025); AXS-05 for Alzheimer’s disease agitation, sNDA submission (3Q 2025); AXS-12 for narcolepsy, NDA submission (2H 2025)."

FDA filing • Launch • Alzheimer's Disease • Fibromyalgia • Migraine • Narcolepsy

Axsome Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Clinical Trial Topline Results: Phase 3 ENGAGE trial of solriamfetol in binge eating disorder (2026); Phase 3 SUSTAIN trial of solriamfetol in shift work disorder (2026). Clinical Trial Initiations and Progress: Pivotal Phase 2/3 trial of AXS-05 in smoking cessation, initiation (2025); Phase 3 trial of solriamfetol in ADHD in pediatric patients, initiation (2025); Phase 3 trial of solriamfetol in MDD with EDS, initiation (2025)."

New P2/3 trial • New P3 trial • P3 data: top line • Attention Deficit Hyperactivity Disorder • Binge Eating Disorder • Major Depressive Disorder

Axsome Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "AUVELITY: Approximately 167,000 prescriptions were written for AUVELITY in the first quarter of 2025, representing an increase of 76% compared to the same period in 2024, and an increase of 5% compared to the fourth quarter of 2024. Payer coverage for AUVELITY across all channels is approximately 78% of all covered lives. The proportion of lives covered for AUVELITY in the commercial and government (Medicare and Medicaid) channels are approximately 63% and 100%, respectively. SUNOSI: Approximately 46,000 prescriptions were written for SUNOSI in the U.S. in the first quarter of 2025, representing an increase of 12% compared to the same period in 2024, and a decrease of 5% compared to the fourth quarter of 2024. Payer coverage for SUNOSI across all channels is approximately 83% of all covered lives. The proportion of lives covered for SUNOSI in the commercial and government channels are approximately 95% and 60%, respectively."

Commercial • CNS Disorders • Major Depressive Disorder • Obstructive Sleep Apnea • Psychiatry • Sleep Disorder

Axsome Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "AUVELITY net product sales were $96.2 million for the first quarter of 2025, representing 80% year-over-year growth. AUVELITY net product sales for the comparable period in 2024 were $53.4 million. SUNOSI net product revenue was $25.2 million for the first quarter of 2025, representing 17% year-over-year growth, which consisted of $24.1 million in net product sales and $1.1 million in royalty revenue associated with SUNOSI sales in out-licensed territories. SUNOSI net product revenue for the comparable period in 2024 was $21.6 million, which consisted of $20.7 million in net product sales and $0.9 million in royalty revenue."

Sales • CNS Disorders • Major Depressive Disorder • Obstructive Sleep Apnea • Psychiatry • Sleep Disorder

Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review. (PubMed, Medicina (Kaunas)) - " The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small...NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with..."

Journal • Monotherapy • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

ACCORD-2: AXS-05 delays relapse time to Alzheimer’s disease agitation (Healio) - P3 | N=456 | ACCORD-2 (NCT04947553) | Sponsor: Axsome Therapeutics, Inc. | "The study included 167 participants aged 65 to 90 years with a clinical diagnosis of probable AD and agitation who received AXS-05 during an open-label period of at least 8 weeks. They were then randomly assigned to continue AXS-05 (n = 83) or placebo (n = 84) for up to 24 weeks. The primary endpoint was the time to AD agitation relapse....Grossberg reported that the study’s primary endpoint was met, with AXS-05 significantly delaying the time to relapse compared with placebo (HR = 0.276; 95% CI, 0.119-0.641). The risk for relapse was 3.6-fold lower in patients who received AXS-05 vs. those who received placebo. Secondary endpoints were also met, with AXS-05 significantly preventing AD agitation relapse (8.4% vs 28.6%) and reducing AD agitation worsening (20.5% vs. 41.7%) compared with placebo."

P3 data • Alzheimer's Disease • Psychomotor Agitation

Efficacy and Safety of AXS-05 in Alzheimer's Disease Agitation: A Phase 3 Randomized Withdrawal Double-Blind Placebo-Controlled Study (AAN 2025) - "AXS-05 prevented worsening of severity of AD agitation and AD overall compared to placebo. AXS-05 was well tolerated, with no new safety signals."

Clinical • Late-breaking abstract • P3 data • Alzheimer's Disease • Anesthesia • CNS Disorders

Pharmacology of novel, fast-acting, non-monoaminergic antidepressants (PubMed, Neuropsychopharmacol Hung) - "Two glutamatergic drugs, esketamine and dextromethorphan-bupropion (AXS-05), have already been approved for the treatment of treatment-resistant depression. The GABAergic drugs brexanolone and zuranolone are approved for the treatment of postpartum depression. These novel treatment options pave the way for novel avenues for further research and new targets in the treatment of depression. Keywords: depression, antidepressant, glutamate, fast-acting antidepressant, non- monoaminergic antidepressant."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Postpartum Depression • Psychiatry

Can dextromethorphan-bupropion reduce mental pain in depressed individuals? A generating hypothesis overview perspective. (PubMed, Ann Gen Psychiatry) - "We hypothesized that dextromethorphan-bupropion could impact the reduction of mental pain in MDD patients by targeting the opioid system, as supported by Panksepp's theory. The combination of dextromethorphan with bupropion might deal with various aspects of mental pain, possibly improving treatment results."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry