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

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

Axsome Therapeutics Announces FDA Pre-NDA Meeting Minutes for AXS-05 in Alzheimer’s Disease Agitation Supporting NDA Submission (GlobeNewswire) - "Axsome Therapeutics, Inc...today announced that it has received formal pre-New Drug Application (NDA) meeting minutes from the U.S. Food and Drug Administration (FDA) supporting a supplemental NDA (sNDA) submission for AXS-05 in Alzheimer’s disease agitation...Based on the feedback from the FDA, the Company’s regulatory data package would be sufficient for the submission of an sNDA for AXS-05 for the treatment of Alzheimer’s disease agitation. Axsome anticipates submitting the planned sNDA in the third quarter of 2025...AXS-05 demonstrated statistically significant improvement in Alzheimer’s disease agitation...in three Phase 3 efficacy trials: the ADVANCE-1 parallel-group trial (p=0.010), the ACCORD-1 randomized withdrawal trial (p=0.014), and the ACCORD-2 randomized withdrawal trial (p=0.001)."

FDA event • FDA filing • Alzheimer's Disease

Axsome Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "AXS-05 demonstrated statistically significant improvements in Alzheimer’s disease agitation compared to placebo in three efficacy trials (ADVANCE-1, ACCORD-1, and ACCORD-2), with supportive efficacy and controlled safety results in a fourth trial (ADVANCE-2). Based on the results from these studies, Axsome plans to submit a New Drug Application (NDA) for AXS-05 for the treatment of Alzheimer’s disease agitation to the FDA in the second half of 2025. Smoking Cessation: Axsome plans to initiate a pivotal Phase 2/3 trial of AXS-05 in smoking cessation in 2025."

FDA filing • New P2/3 trial • Alzheimer's Disease

Axsome Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Auvelity net product sales were $92.6 million and $291.4 million for the fourth quarter and full year of 2024, representing 89% and 124% year-over-year growth, respectively. Auvelity net product sales for the comparable periods in 2023 were $49.0 million and $130.1 million, respectively. Sunosi net product revenues were $26.2 million and $94.3 million for the fourth quarter and full year of 2024, representing 16% and 26% year-over-year growth, respectively, which consisted of $24.7 million and $90.3 million in net products sales and $1.4 million and $4.0 million in royalty and milestone revenue associated with Sunosi sales in out-licensed territories, respectively."

Sales • Cataplexy • CNS Disorders • Depression • Excessive Daytime Sleepiness • Excessive Daytime Sleepiness in Narcolepsy • Major Depressive Disorder • Mood Disorders • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Sleep Disorder

Axsome Therapeutics Announces Settlement Agreement Resolving AUVELITY (dextromethorphan HBr – bupropion HCl) Patent Litigation (GlobeNewswire) - "Axsome Therapeutics, Inc...today announced that it has entered into a settlement agreement with Teva Pharmaceuticals, Inc. (Teva) resolving all patent litigation related to Axsome’s AUVELITY (dextromethorphan HBr – bupropion HCl) product. The litigation resulted from submission by Teva of an Abbreviated New Drug Application to the U.S. Food and Drug Administration (FDA) seeking approval to market a generic version of AUVELITY in the United States prior to the expiration of applicable Axsome patents. Under the terms of the settlement agreement, Axsome will grant Teva a license to sell its generic version of AUVELITY beginning on or after March 31, 2039, if pediatric exclusivity is granted for AUVELITY, or on or after September 30, 2038, if no pediatric exclusivity is granted, subject to FDA approval and conditions and exceptions customary for agreements of this type."

Commercial • CNS Disorders

AXS-05-AD-303: A Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Alzheimer's Disease Agitation (clinicaltrials.gov) - P3 | N=456 | Completed | Sponsor: Axsome Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=300 ➔ 456

Enrollment change • Trial completion • Alzheimer's Disease • CNS Disorders • Dementia

ADVANCE-2: A Study to Assess the Efficacy and Safety of AXS-05 in Subjects with Alzheimer's Disease Agitation (clinicaltrials.gov) - P3 | N=408 | Completed | Sponsor: Axsome Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Dementia

Drug Development. (PubMed, Alzheimers Dement) - P2/3, P3 | "AXS-05 demonstrated a substantial, rapid reduction in ADA vs controls after 5 weeks of treatment, increased time-to-relapse vs placebo, and was well-tolerated, supporting its development as a promising treatment option for ADA."

Clinical • Journal • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Summary of Topline Results of the ACCORD-2 Phase 3 Trial (GlobeNewswire) - P3 | N=300 | ACCORD-2 (NCT04947553) | Sponsor: Axsome Therapeutics, Inc. | "Treatment with AXS-05 was associated with a mean reduction from baseline in the CMAI total score of 20.4 points at Week 6, representing a 46% reduction from the mean baseline score. Clinical response on the CMAI (defined as ≥30% reduction from baseline) after treatment with AXS-05 was achieved by 69% of patients at Week 6, after treatment with AXS-05. Improvement in Alzheimer's disease agitation, assessed using the clinician rated modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), was achieved by 78% of patients at Week 6, after treatment with AXS-05. Improvement in Alzheimer's disease agitation, assessed using the caregiver rated Patient Global Impression of Change (PGI-C), was achieved by 71% of patients at Week 4, and 78% of patients at Week 8, after treatment with AXS-05....The Company plans to submit a New Drug Application (NDA) to the FDA in 2H 2025."

FDA filing • P3 data: top line • Alzheimer's Disease

Summary of Topline Results of the ADVANCE-2 Phase 3 Trial (GlobeNewswire) - P3 | N=350 | ADVANCE-2 (NCT05557409) | Sponsor: Axsome Therapeutics, Inc. | "The study did not demonstrate statistical significance for the primary endpoint, change in the CMAI total score from baseline to Week 5 (CMAI reductions of 13.8 and 12.6 points for AXS-05 and placebo, respectively). Results of the primary endpoint and almost all secondary endpoints numerically favored AXS-05 over the placebo group. The overall rates of adverse event in ADVANCE-2 were 26.0% in the AXS-05 group and 21.6% in the placebo group. The most common adverse events were dizziness (5.9% for AXS-05 and 1.5% for placebo), and headache (4.4% for AXS-05 and 3.4% placebo). One subject (0.5%) each in the AXS-05 and placebo groups experienced falls, which was deemed not related to study medication for the subject in the AXS-05 group."

P3 data: top line • Alzheimer's Disease

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

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

ADVANCE-2: A Study to Assess the Efficacy and Safety of AXS-05 in Subjects with Alzheimer's Disease Agitation (clinicaltrials.gov) - P3 | N=350 | Active, not recruiting | Sponsor: Axsome Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Dec 2024 | Trial primary completion date: Jun 2025 ➔ Dec 2024

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

AXS-05-AD-303: A Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects with Alzheimer's Disease Agitation (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Axsome Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia

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=150 | Enrolling by invitation | Sponsor: Axsome Therapeutics, Inc.

New P3 trial • Alzheimer's Disease • CNS Disorders • Dementia

Eco-friendly bupropion detection sensor with co-formulated dextromethorphan in AUVELITY tablet and spiked plasma. (PubMed, Sci Rep) - "A linear and repeatable response was displayed by the sensor across a range of 1.0 × 10⁻13 M to 1.0 × 10⁻11 M of BUP, with a limit of detection of 3.18 × 10⁻14 M. The sensor demonstrated robust selectivity for BUP over interfering drugs, such as dextromethorphan, in pharmaceutical dosage forms and spiked human plasma. The environmental impact of the proposed approach was evaluated using green analytical chemistry principles, including the Green Analytical Procedure Index (GAPI) and the Analytical GREEnness (AGREE) metric."

Journal

Axsome Therapeutics Presents Data from Its Leading Neuroscience Pipeline at NEI Congress 2024 (GlobeNewswire) - "Axsome Therapeutics, Inc...today announced eight presentations spanning its innovative portfolio of late-stage products and product candidates in psychiatry and neurology at NEI Congress 2024, being held Nov. 7 - Nov. 10, 2024, in Colorado Springs, Colorado."

P2/3 data • Alzheimer's Disease • CNS Disorders

Axsome Therapeutics Presents Data from Multiple Programs Spanning Its Innovative Neuroscience Portfolio at Psych Congress 2024 (GlobeNewswire) - "Axsome Therapeutics, Inc...today announced seven presentations from across its broad portfolio of innovative neuroscience products and product candidates at Psych Congress 2024, being held Oct. 29 - Nov. 2, 2024, in Boston, Massachusetts."

P2/3 data • Alzheimer's Disease • CNS Disorders