Axsome Therapeutics, Inc. (Axsome) operates as a biopharmaceutical company.
The company is leading a new era in the treatment of CNS disorders. The company is dedicated to the development and delivery of transformative medicines for people impacted by central nervous system, or CNS, conditions. The company delivers scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in pa...
Axsome Therapeutics, Inc. (Axsome) operates as a biopharmaceutical company.
The company is leading a new era in the treatment of CNS disorders. The company is dedicated to the development and delivery of transformative medicines for people impacted by central nervous system, or CNS, conditions. The company delivers scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes.
The company’s CNS portfolio includes three approved products – Auvelity (the components of which are referred to as ‘AXS-05’), Sunosi (the components of which are referred to as ‘solriamfetol’), both of which are also being developed for further indications, and Symbravo (the components of which are referred to as ‘AXS-07’), which was recently approved by the U.S. Food and Drug Administration (FDA) on January 30, 2025, as well as two product candidates, AXS-12, and AXS-14, which are being developed for multiple indications. The company refers herein to Auvelity, Sunosi, Symbravo, AXS-12, AXS-14, and its programs to develop additional indications for AXS-05 and solriamfetol as its products.
Pipeline
The company’s pipeline consists of three commercial products for major depressive disorder, or MDD, and excessive daytime sleepiness, or EDS, associated with narcolepsy and obstructive sleep apnea, its recently FDA-approved product for the acute treatment of migraine, as well as multiple innovative, late-stage, patent-protected product candidates addressing a broad range of serious neurological and psychiatric conditions that collectively impact over 150 million people in the United States. The company is leveraging its deep expertise and experience in neuroscience to maximize the potential of its approved products for additional CNS conditions, as well as advance its novel product candidates that it offers distinct advantages over available therapies.
Commercial Products
Auvelity: Auvelity (dextromethorphan-bupropion) is a novel, oral, N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 receptor agonist, aminoketone, and CYP2D6 inhibitor indicated for the treatment of MDD in adults. Auvelity was developed by the company and approved by the U.S. Food and Drug Administration, or FDA, for the treatment of MDD in adults in August 2022. Th e company initiated the commercial launch of Auvelity in the United States in October 2022. The company refers to the proprietary dextromethorphan-bupropion formulation contained in Auvelity as AXS-05. As used in this report, ‘Auvelity’ refers to AXS-05 approved by the FDA for the treatment of MDD in adults, and ‘AXS-05’ refers to AXS-05 in development programs for the treatment of indications beyond MDD in adults.
Sunosi: Sunosi (solriamfetol) is a novel, oral, dopamine and norepinephrine reuptake inhibitor (DNRI), trace amine-associated receptor 1 (TAAR1) agonist, and 5-HT1A agonist indicated for the treatment of EDS in patients with narcolepsy or obstructive sleep apnea, or OSA. Sunosi was approved for the treatment of EDS in the United States in 2019 and by the European Commission in 2022. The company acquired the U.S. rights to Sunosi from Jazz Pharmaceuticals plc, or Jazz, in May 2022 and the ex-U.S. rights (excluding certain Asian markets) from Jazz in November 2022. The company has been commercializing Sunosi it completed these acquisitions. SK Biopharmaceuticals Co. Ltd., or SK, is the originator of Sunosi and retains rights in 12 Asian markets, including China, Korea, and Japan. The company refers to the acquisition of Sunosi herein as the Acquisition. In February 2023, the company entered into a licensing agreement, or the Pharmanovia License Agreement, with Atnahs Pharma UK Limited, or Pharmanovia, that granted to Pharmanovia the exclusive right to market Sunosi in Europe and certain countries in the Middle East and North Africa, referred to as the Licensed Territory. As used in this report, ‘Sunosi’ refers to solriamfetol approved for the treatment of EDS in patients with narcolepsy or OSA, and ‘solriamfetol’ refers to solriamfetol in development programs for the treatment of indications beyond EDS in patients with narcolepsy or OSA.
Symbravo: Symbravo (MoSEIC meloxicam rizatriptan), or AXS-07, is a novel, oral, rapidly absorbed, multi-mechanistic, selective COX-2 inhibitor and 5-HT1B/1D agonist indicated for the acute treatment of migraine with or without aura. Symbravo was developed by the company and approved by the FDA for the acute treatment of migraine with or without aura in adults in January 2025.
Development Programs
AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist, sigma-1 receptor agonist, aminoketone, and CYP2D6 inhibitor being developed for the treatment of Alzheimer’s disease agitation, or AD agitation, and smoking cessation. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. AXS-05 has been granted FDA Breakthrough Therapy designation for AD agitation. In December 2024,the company announced the successful completion of its Phase 3 clinical program of AXS-05 in AD agitation, which consists of the ADVANCE-1 Phase 2/3 trial, ADVANCE-2 Phase 3 trial, ACCORD-1 Phase 3 trial, and ACCORD-2 Phase 3 trial evaluating the efficacy and safety of AXS-05 in patients with AD agitation, as well as an open-label extension trial evaluating the long-term safety of AXS-05. A positive Phase 2 trial of AXS-05 in smoking cessation has been completed under a research collaboration with Duke University.
AXS-12 (reboxetine) is a novel, oral, investigational, highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator being developed for the treatment of narcolepsy. AXS-12 has been granted FDA Orphan Drug Designation for narcolepsy. The company’s clinical program for AXS-12 in narcolepsy includes its completed positive CONCERT Phase 2 trial and SYMPHONY Phase 3 trial evaluating the efficacy and safety of AXS-12 compared to placebo, as well as the company’s completed positive ENCORE Phase 3 trial evaluating the long-term efficacy and safety of AXS-12 in patients with narcolepsy with cataplexy.
AXS-14 (esreboxetine) is a novel, oral, investigational, highly selective and potent norepinephrine reuptake inhibitor being developed for the management of fibromyalgia. Esreboxetine, the SS-enantiomer of reboxetine, is more potent and selective than racemic reboxetine. The company has in-licensed data from Pfizer Inc., or Pfizer, which includes a completed positive Phase 2 and Phase 3 trial in fibromyalgia.
Solriamfetol is an oral, dopamine and norepinephrine reuptake inhibitor (DNRI), trace amine-associated receptor 1 (TAAR1) agonist, and 5-HT1A agonist being developed for the treatment of attention deficit hyperactivity disorder, or ADHD, major depressive disorder, or MDD, binge eating disorder, or BED, and excessive sleepiness associated with shift work disorder, or SWD. The company is conducting four Phase 3, randomized, double-blind, placebo-controlled, multicenter trials evaluating the efficacy and safety of solriamfetol in each of these indications, including the FOCUS study in attention deficit hyperactivity disorder (ADHD), the PARADIGM study in MDD, the ENGAGE study in BED, and the SUSTAIN study in SWD. Additionally, the company is evaluating other product candidates that it intends to develop for CNS disorders.
The company’s product candidates are protected by a combination of patents, trade secrets, and proprietary know-how. If approved, they may also be eligible for periods of regulatory exclusivity. The company’s intellectual property portfolio includes issued U.S. and foreign, patents with claims extending to 2034, 2040, 2041, and 2043 for AXS-05 and to 2039 for AXS-12, as well as the United States (U.S.) and foreign patent applications for AXS-05, AXS-12, and AXS-14. The company’s issued U.S. and foreign patents for Symbravo include claims extending out to 2040. The company’s Orange Book listed patents in the United States for Sunosi extend out to 2042. The company also has patents in various other countries pertaining to Sunosi. In June 2024, the company entered into a settlement agreement with Unichem Laboratories Ltd., or Unichem, resolving patent litigation related to Sunosi that permits Unichem to begin selling its generic version of Sunosi on June 30, 2042, or earlier under certain circumstances. In August 2024, the company reached an agreement with Sandoz Inc., or Sandoz, to dismiss the patent litigation related to Sunosi following Sandoz’s withdrawal of its Abbreviated New Drug Application, or ANDA, for a generic equivalent of Sunosi. As a result, the litigation has been dismissed without prejudice. In February 2025, the company entered into a settlement agreement resolving all outstanding patent litigation related to Auvelity. The litigation resulted from submission by Teva of an ANDA to the FDA seeking approval to market a generic version of Auvelity in the U.S. 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, 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.
Strategy
The primary elements of the company’s strategy include pursuing novel CNS indications with high unmet medical need; developing products with its proprietary medicinal chemistry and formulation technologies; developing products with differentiated profiles; reducing clinical and regulatory risk, and accelerate time to market; and retaining commercial rights in the United States, where appropriate, and selectively partner outside of the United States to maximize the value of its product candidates.
CNS Product Candidates
AXS-05
AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist, sigma-1 receptor agonist, aminoketone, and CYP2D6 inhibitor being developed for the treatment of CNS disorders. AXS-05 consists of a proprietary formulation and dose of dextromethorphan and bupropion and utilizes Axsome’s metabolic inhibition technology. The dextromethorphan component of AXS-05 is an uncompetitive antagonist of the NMDA receptor, an ionotropic glutamate receptor, and a sigma-1 receptor agonist. Dextromethorphan is quickly eliminated from the body following administration due to extensive first pass metabolism, which results in low blood levels even at high doses. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan by inhibiting its metabolism and is also a dopamine and norepinephrine reuptake inhibitor (DNRI). Based on its unique mechanism of action with multimodal activity, the company’s AXS-05 has potential therapeutic benefit for a variety of CNS disorders.
The company is developing AXS-05 for the treatment of AD agitation and smoking cessation.
Alzheimer’s Disease (AD) Agitation
In June 2020, the company announced that AXS-05 had received FDA Breakthrough Therapy designation for AD agitation. In August 2020, the company announced confirmation of the pivotal development status and plan for AXS-05 for the treatment of AD agitation following a Breakthrough Therapy meeting with the FDA. In December 2024, the company announced the successful completion of its Phase 3 clinical program of AXS-05 in AD agitation, which consists of the ADVANCE-1 Phase 2/3 trial, ADVANCE-2 Phase 3 trial, ACCORD-1 Phase 3 trial, and ACCORD-2 Phase 3 trial evaluating the efficacy and safety of AXS-05 in patients with AD agitation, as well as an open-label extension trial evaluating the long-term safety of AXS-05 in AD agitation.
ADVANCE-1 Study
In July 2017, the company initiated the ADVANCE-1 study, a Phase 2/3, randomized, double-blind, controlled, multicenter U.S. trial to evaluate the efficacy and safety of AXS-05 in patients with AD agitation. A total of 366 patients with a diagnosis of probable AD and clinically meaningful agitation associated with their AD were 1:1 randomized to receive AXS-05 (dextromethorphan-bupropion tablet, dose escalated to 45 mg-105 mg twice daily), bupropion (dose escalated to 105 mg twice daily), or matching placebo for 5 weeks. An independent data monitoring committee performed an interim futility analysis and recommended no further randomization to the bupropion arm. Subsequently, patients were 1:1 randomized to receive AXS-05 or placebo. The primary endpoint was the change from baseline in the Cohen-Mansfield Agitation Inventory, or CMAI, total score compared to placebo at Week 5. In April 2020, the company announced that AXS-05 achieved the primary endpoint and rapidly and substantially improved agitation in patients with AD.
AXS-05 was well tolerated in the ADVANCE-1 trial. The most common adverse events were somnolence (8.2% for AXS-05 vs. 4.1% for bupropion vs. 3.2% for placebo), dizziness (6.3% for AXS-05 vs. 10.2% for bupropion vs. 3.2% for placebo), and diarrhea (4.4% for AXS-05 vs. 6.1% for bupropion vs. 4.4% for placebo).
ACCORD-1 Study
In December 2020, the company initiated the ACCORD-1 study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of AXS-05 in patients with AD agitation. The trial consisted of a 9-week, open-label period during which patients were treated with AXS-05 and monitored for a sustained clinical response, followed by a 26-week, double-blind, placebo-controlled, randomized withdrawal period. Sustained clinical response was defined as a =30% improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change, or PGI-C, scale (score of =3) that were maintained for at least 4 consecutive weeks. A total of 178 patients were enrolled into the open-label period and treated with AXS-05, and 108 patients were 1:1 randomized to continue AXS-05 (n=53) or to switch to placebo (n=55) for up to 26 weeks or until a relapse of agitation occurred. Relapse was defined as a =10-point worsening in the CMAI total score from randomization, or a CMAI total score greater than that at study entry, or hospitalization or other institutionalization due to AD agitation. The primary endpoint was the time from randomization to relapse of AD agitation calculated by Kaplan-Meier estimates and the hazard ratio. Secondary assessments included the CMAI, clinician- and caregiver-rated scales, and safety parameters. The key secondary endpoint was the percentage of patients who relapsed compared to placebo.
In November 2022, the company announced that AXS-05 achieved the primary endpoint in the ACCORD-1 Phase 3 trial by substantially and statistically significantly delaying the time to relapse of AD agitation compared to placebo, with a hazard ratio for time to relapse of 0.275 (p=0.014), representing a 3.6-fold lower risk of relapse compared to placebo. AXS-05 also met the key secondary endpoint by statistically significantly preventing relapse of AD agitation compared to placebo, with 7.5% of patients in the AXS-05 group relapsing compared to 25.9% of patients in the placebo group (p=0.018). In the open-label treatment period, AXS-05 demonstrated a rapid, substantial, and statistically significant improvement in AD agitation compared to baseline as measured by the CMAI total score, starting at Week 1 and continuing throughout at all timepoints (p<0.001). Additionally, rapid and substantial improvement in AD agitation was reported by both clinicians and caregivers on global measures. Clinicians reported improvement in AD agitation with open-label AXS-05 treatment in 66% of patients at 2 weeks and 86% at 5 weeks as measured by the mADCS-CGIC scale. Caregivers reported improvement in AD agitation in 68% of patients at 2 weeks and 89% at 5 weeks as measured by the PGI-C scale.
AXS-05 was well tolerated in the ACCORD-1 trial. The rates of adverse events in the double-blind period were 28.3% in the AXS-05 group and 22.2% in the placebo group. Discontinuation rates due to adverse events were low (0% for AXS-05 vs. 1.9% for placebo). One serious adverse event was reported in the AXS-05 group (faecaloma), which was determined by the investigator to be not related to the study drug, and two serious adverse events were reported in the placebo group (cardiac arrest, femur fracture). Falls were reported in four patients in the AXS-05 group, none of which were associated with serious adverse events and all of which were determined by the investigators to be not related to the study drug, and in two patients in the placebo group, one of which was associated with a femur fracture. There were no deaths in the AXS-05 group and one death in the placebo group. AXS-05 was not associated with sedation or cognitive decline as measured by the MMSE.
ADVANCE-2 Study
In September 2022, the company initiated the ADVANCE-2 study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of AXS-05 in patients with AD agitation. A total of 408 patients were 1:1 randomized to receive AXS-05 (dextromethorphan-bupropion tablet, dose escalated to 45 mg-105 mg twice daily) or matching placebo for 5 weeks. In December 2024, the company announced topline results from the ADVANCE-2 trial. AXS-05 did not achieve statistical significance for the primary endpoint, the change in the CMAI total score compared to placebo at Week 5, with mean reductions from baseline of 13.8 points for AXS-05 and 12.6 points for placebo. However, results for the primary and nearly all secondary endpoints numerically favored AXS-05 placebo at all time points in the trial.
AXS-05 was safe and well tolerated in the ADVANCE-2 trial. The rates of adverse events in the trial 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 vs. 1.5% for placebo) and headache (4.4% for AXS-05 vs. 3.4% for placebo).
ACCORD-2 Study
In May 2024, the company announced that it had initiated the ACCORD-2 study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of AXS-05 in patients with AD agitation. The trial consisted of an open-label treatment period followed by a 24-week, double-blind, placebo-controlled, randomized withdrawal period.
In December 2024, the company announced that AXS-05 achieved the primary endpoint in the ACCORD-2 Phase 3 trial and demonstrated a highly statistically significant delay in the time to relapse of AD agitation compared to placebo, with a hazard ratio for time to relapse of 0.276 (p=0.001), representing a 3.6-fold lower risk of relapse compared to placebo. AXS-05 also met the key secondary endpoint by statistically significantly preventing relapse of AD agitation compared to placebo, with 8.4% of patients in the AXS-05 group relapsing compared to 28.6% of patients in the placebo group (p=0.001).
AXS-05 was safe and well tolerated in the ACCORD-2 trial.
Long-Term Safety Study
In December 2024, the company announced topline results from the open-label extension trial evaluating the long-term safety and tolerability of AXS-05 in patients with AD agitation. A total of 456 patients were treated with AXS-05 for up to 12 months. AXS-05 was well tolerated with long-term dosing, with a safety profile consistent with the controlled efficacy and safety trials.
Smoking Cessation
The company is also evaluating AXS-05 as an aid to smoking cessation treatment.
In December 2017, the company entered into a research collaboration agreement with Duke University to evaluate AXS-05 in a Phase 2 clinical trial in smoking cessation under an Investigator Sponsored Investigational New Drug Application, or IND. In April 2018, the company announced the enrollment of the first patient into a Phase 2 clinical trial of AXS-05 for smoking cessation treatment, which was being conducted under its research collaboration agreement with Duke University. In April 2019, the company announced that AXS-05 met the prespecified primary endpoint in the Phase 2 trial in smoking cessation. In November 2021, the company announced that it had received from the FDA positive Pre-Investigational New Drug Application, or Pre-IND, meeting written guidance on a proposed clinical developmental plan for AXS-05 as an aid to smoking cessation. Based on this feedback, Axsome plans to proceed to a pivotal Phase 2/3 trial in this indication.
AXS-12
AXS-12 (reboxetine) is a novel, oral, potent, highly selective investigational norepinephrine reuptake inhibitor and cortical dopamine modulator being developed for the treatment of narcolepsy.
In October 2018, the company received Orphan Drug Designation from the FDA for AXS-12 for the treatment of narcolepsy. In January 2020, the company entered into an exclusive license agreement with Pfizer for Pfizer’s clinical and nonclinical data, and intellectual property for reboxetine, the active pharmaceutical ingredient in AXS-12. In September 2020, the company announced that the Phase 2 CONCERT study and a single Phase 3 study would be sufficient to support the filing of an NDA. In July 2021, the company announced that it was notified by the FDA that the FDA had rescinded its Breakthrough Therapy Designation for AXS-12 for the treatment of cataplexy in narcolepsy, due to the FDA’s approval of an additional drug product for the treatment of cataplexy in narcolepsy subsequent to their granting AXS-12 Breakthrough Therapy designation.
Narcolepsy
Narcolepsy is a serious and debilitating orphan neurological condition that causes dysregulation of the sleep-wake cycle and is characterized clinically by EDS, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep.
The company’s clinical program for AXS-12 in narcolepsy includes its completed positive CONCERT Phase 2 trial and SYMPHONY Phase 3 trial evaluating the efficacy and safety of AXS-12 compared to placebo, as well as its completed positive ENCORE Phase 3 trial evaluating the long-term efficacy and safety of AXS-12 in patients with narcolepsy with cataplexy.
CONCERT Study
In January 2019, the company initiated the CONCERT study to evaluate the efficacy and safety of AXS-12 in narcolepsy. In December 2019, the company announced that AXS-12 met the prespecified primary endpoint and significantly reduced the total number of cataplexy attacks compared to placebo.
CONCERT was a Phase 2, randomized, double-blind, placebo-controlled, crossover, multicenter, U.S. trial in which 21 patients with a diagnosis of narcolepsy with cataplexy were all treated with orally administered AXS-12 for 2 weeks, and with placebo for 2 weeks, with the treatment periods separated by 1 week of down-titration and washout.
AXS-12 met the prespecified primary endpoint by demonstrating a highly statistically significant reduction from baseline in the mean weekly number of cataplexy attacks, averaged for the 2-week treatment period, the overall treatment effect, compared to placebo (p<0.001). AXS-12 significantly improved EDS symptoms compared to placebo, as measured by the Epworth Sleepiness Scale, or ESS, and by the frequency of inadvertent naps. AXS-12 significantly improved sleep quality, as measured by overall improvement and by number of awakenings at night, and reduced sleep-related symptoms, compared to placebo.
AXS-12 was well tolerated in the trial. The most common adverse events in the AXS-12 group were anxiety, constipation, and insomnia.
SYMPHONY Study
In September 2021, the company enrolled the first patient in SYMPHONY study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of AXS-12 in patients with narcolepsy. A total of 90 patients were 1:1 randomized to receive AXS-12 or placebo for 5 weeks. Patients took either AXS-12 (5 mg) or placebo once daily during Week 1 followed by twice daily dosing during Weeks 2-5. The primary endpoint was the change in frequency of weekly cataplexy attacks. Other symptoms of narcolepsy, as well as safety and tolerability were also assessed in the trial. In March 2024, the company announced that AXS-12 achieved the primary endpoint in the SYMPHONY Phase 3 trial and statistically significantly reduced the frequency of cataplexy attacks in patients with narcolepsy compared to placebo. AXS-12 also reduced EDS severity, improved cognitive function, and reduced overall narcolepsy severity compared to placebo.
AXS-12 met the primary endpoint by demonstrating a substantial and statistically significant reduction from baseline in weekly cataplexy attacks compared to placebo at Week 5. AXS-12 significantly reduced EDS severity as measured by the Clinical Global Impression of Severity (CGI-S) scale for EDS compared to placebo at Week 5. AXS-12 significantly improved concentration and memory compared to placebo at Week 5 as measured by the Cognitive Function Items of the Functional Outcomes of Sleep Questionnaire.
AXS-12 also demonstrated improvements in overall narcolepsy, patient function, and quality of life. Clinicians reported a rapid and significant reduction in overall narcolepsy severity in patients in the AXS-12 group compared to patients in the placebo group, as measured by the CGI-S for narcolepsy, at Week 5 (p=0.007), with improvements observed as early as Week 1.
ENCORE Study
In October 2021, the company initiated the ENCORE study, a Phase 3, randomized, double-blind, placebo-controlled trial to evaluate the long-term efficacy and safety of AXS-12 in patients with narcolepsy. The trial consisted of a 24-week open-label treatment period followed by a 3-week, double-blind, randomized withdrawal period. A total of 68 patients, who rolled over from the SYMPHONY Phase 3 trial, were enrolled into the open-label period and treated with AXS-12 (5 mg) once-daily for the first week, followed by twice-daily dosing for the subsequent 23 weeks. Patients who completed the open-label treatment period (n=42) were then 1:1 randomized to continue AXS-12 (n=22) or to switch to placebo (n=20). The primary endpoint was the change in frequency of weekly cataplexy attacks from randomization to week 3 of the double-blind period. Other symptoms of narcolepsy, as well as safety and tolerability were also assessed throughout the trial. In March 2024, the company announced that AXS-12 achieved the primary endpoint in the SYMPHONY Phase 3 trial and statistically significantly reduced the frequency of cataplexy attacks in patients with narcolepsy compared to placebo. AXS-12 also reduced EDS severity, improved cognitive function, and reduced overall narcolepsy severity compared to placebo.
AXS-12 met the primary endpoint of the change from randomization in the frequency of cataplexy attacks compared to placebo at week 3 of the double-blind period. Patients randomized to switch to placebo experienced a statistically significant worsening in the average weekly number of cataplexy attacks compared to patients randomized to continue AXS-12 treatment, with an increase of 10.29 attacks per week for placebo compared to 1.32 attacks per week for AXS-12, at 3 weeks (p=0.017).
AXS-14
AXS-14 (esreboxetine) is a novel, oral, potent, highly selective investigational norepinephrine reuptake inhibitor being developed for the management of fibromyalgia. Esreboxetine, the SS-enantiomer of reboxetine, is more potent and selective than racemic reboxetine.
In January 2020, the company received from Pfizer an exclusive license to develop and commercialize esreboxetine in the U.S. for fibromyalgia and other indications. The license encompasses nonclinical and clinical data for esreboxetine, including results from a positive Phase 3 and a positive Phase 2 trial of esreboxetine in the treatment of fibromyalgia conducted by Pfizer.
Fibromyalgia
Fibromyalgia is a chronic disorder often characterized by widespread musculoskeletal pain, fatigue, disturbed sleep, depression, and cognitive impairment. Other symptoms of this disorder can include tingling in the hands and feet and headaches. Fibromyalgia is considered to be mediated mainly in the central nervous system. Approximately 17 million people in the U.S. suffer from fibromyalgia. Treatment options for fibromyalgia are limited with only three pharmacologic treatments approved by the FDA.
In a Phase 3 trial conducted by Pfizer in 1,122 patients with fibromyalgia treated with esreboxetine or placebo for 14 weeks, esreboxetine met the two primary endpoints by demonstrating statistically significant improvements in the weekly mean pain score compared to placebo (p<0.001, p<0.001, and p=0.025 for 4 mg, 8 mg and 10 mg daily doses, respectively), and the Fibromyalgia Impact Questionnaire, or FIQ, total score (p<0.001, p<0.001, and p=0.023 for 4 mg, 8 mg and 10 mg daily doses, respectively). Esreboxetine also resulted in statistically significant improvements in patient-reported global functioning compared to placebo as measured by the PGI-C scale (p=0.002, p=0.001, and p=0.007 for 4 mg, 8 mg and 10 mg daily doses, respectively), and in fatigue as measured by the Global Fatigue Index (p=0.001 and p=0.001 for 4 mg and 8 mg daily doses, respectively).
In a Phase 2 trial conducted by Pfizer in 267 patients with fibromyalgia treated with esreboxetine (dose escalated to 8 mg/day) or placebo for 8 weeks, esreboxetine met the primary endpoint by demonstrating statistically significant improvements in the weekly mean pain score compared to placebo (p=0.006). The study also demonstrated statistically significant improvements in additional efficacy outcomes, including the FIQ total score (p<0.001), the PGI-C scale (p<0.001), and fatigue as measured by the Multidimensional Assessment of Fatigue scale (p<0.001).
Solriamfetol
Solriamfetol is an oral, DNRI, TAAR1 agonist, and 5-HT1A agonist being developed for the treatment of CNS disorders. The company is developing solriamfetol in ADHD, MDD, binge eating disorder (BED), and SWD.
Attention Deficit Hyperactivity Disorder
ADHD is a chronic neurobiological and developmental disorder characterized by a persistent pattern of inattention, hyperactivity, or impulsivity that interferes with functioning or development. Impairments in cognition are apparent in attention, planning and problem solving, working memory, and behavioral inhibition.
FOCUS Study
In July 2023, the company initiated the FOCUS study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of solriamfetol for the treatment of ADHD in adults. Approximately 450 patients will be randomized in a 1:1:1 ratio to receive solriamfetol (150 mg or 300 mg) or placebo for 6 weeks. The primary endpoint is the change in the Adult ADHD Investigator Symptom Report Scale, or AISRS.
Major Depressive Disorder
MDD is a debilitating, chronic, biologically based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, which impair social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. MDD is one of the most common mental disorders in the U.S. where approximately 1 in 5 individuals will experience MDD at some point in their life. According to the U.S. Department of Health and Human Services, or HHS, an estimated 21 million adults in the U.S. experience MDD each year. In addition, according to the World Health Organization, or WHO, depression is the leading cause of disability worldwide and is a major contributor to the overall global burden of disease. Over 70% of patients experience only a partial improvement in symptoms with first-line standard of care.
PARADIGM Study
In March 2024, the company initiated the PARADIGM study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of solriamfetol for the treatment of MDD in adults. Approximately 300 patients will be randomized in a 1:1 ratio to receive solriamfetol (300 mg) or placebo for 6 weeks. The primary endpoint is the change in the Montgomery Åsberg Depression Rating Scale, or MADRS.
Binge Eating Disorder
BED is the most common eating disorder, affecting an estimated 7 million people in the U.S. While BED is 1.75 times more common in women than men, it is still more common in men than other eating disorders. BED is thought to involve issues with food reward processing, impulse control, and appetite regulation, and is associated with a 2- to 3-fold increased risk of psychiatric or medical comorbidities. Most people with BED remain untreated with approximately one quarter of patients having received treatment in the past year and less than half receiving treatment in their lifetime. Treatment options are limited, with only one product currently approved for the treatment of BED. In November 2023, the company announced that it had received from the FDA positive Pre-IND meeting written guidance on a proposed clinical developmental plan for solriamfetol in BED. In November 2023, the company announced that it had received from the FDA positive Pre-IND meeting written guidance on a proposed clinical developmental plan for solriamfetol in BED.
ENGAGE Study
In April 2024, the company initiated the ENGAGE study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of solriamfetol for the treatment of BED in adults. Approximately 450 patients will be randomized in a 1:1:1 ratio to receive solriamfetol (150 or 300 mg) or placebo for 12 weeks. The primary endpoint is the change in days with binge eating episodes.
Shift Work Disorder
In November 2023, the company announced that it had received from the FDA positive Pre-IND meeting written guidance on a proposed clinical developmental plan for solriamfetol for ES associated with SWD.
SUSTAIN Study
In August 2024, the company announced it had initiated the SUSTAIN study, a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of solriamfetol for the treatment of SWD in adults. Approximately 450 patients will be randomized in a 1:1:1 ratio to receive solriamfetol (150 or 300 mg) or placebo for 12 weeks. The primary endpoint is the change in the CGI-C score.
Pain and Primary Care
The company continues to own and maintain the intellectual property covering its pain and primary care assets that it is not developing.
Material License Agreements
Exclusive License Agreement with Pfizer
In January 2020, the company entered into an agreement with Pfizer for an exclusive U.S. license to Pfizer’s clinical and nonclinical data, and intellectual property for reboxetine, the active pharmaceutical ingredient in AXS-12 which Axsome is developing for the treatment of narcolepsy. The agreement also provides Axsome exclusive rights to develop and commercialize esreboxetine, a new late-stage product candidate referred to as AXS-14, in the U.S. for the treatment of fibromyalgia. Under the terms of the agreement, the company received from Pfizer an exclusive U.S. license to Pfizer data for reboxetine and esreboxetine encompassing a full range of nonclinical studies, and short-term and long-term clinical trials involving more than five thousand patients. The licensed data includes results of a positive Phase 3 and a positive Phase 2 trial of esreboxetine in the treatment of fibromyalgia. The company will have the exclusive right and sole responsibility of developing AXS-14 (esreboxetine) in the U.S. for the treatment of fibromyalgia and for other indications.
Exclusive License Agreements with Antecip
In 2012, the company entered into three exclusive license agreements with Antecip Bioventures II LLC, or Antecip, an entity owned by its Chief Executive Officer and Chairman of the Board of Directors, or the Board, Herriot Tabuteau, M.D., in which it were granted exclusive licenses to develop, manufacture, and commercialize Antecip’s patents and applications related to the development of AXS-05 anywhere in the world for veterinary and human therapeutic and diagnostic use, and additional patents and applications that are not relevant to its programs in development. The agreements were amended in August 2015 to update the schedule of patents and applications subject to the license agreements. Pursuant to the agreements, the company are required to use commercially reasonable efforts to develop, obtain regulatory approval for, and commercialize AXS-05.
Royalty Agreement with Jazz Pharmaceuticals, SK Biopharmaceuticals Co., Ltd. and Aerial Biopharma, LLC
In connection with the Acquisition, in addition to the upfront purchase price, the company assumed certain liabilities in connection with the Acquisition and agreed to make non-refundable, non-creditable royalty payments to Jazz on U.S. net sales. There are no royalty payments due to Jazz for net sales outside of the U.S. In addition, the company assumed all of the commitments of Jazz to SK and Aerial Biopharma, LLC, or Aerial.
Pharmanovia
In February 2023, the company announced a licensing transaction with Pharmanovia to market Sunosi in Europe and certain countries in the Middle East / North Africa.
Intellectual Property
As of February 11, 2025, the company’s intellectual property portfolio contained more than 600 issued patents and more than 400 pending applications in the United States and worldwide. More than 140 issued United States patents and more than 91 issued foreign patents cover the company’s AXS-05 product candidate, which has claims covering method of treatment, pharmaceutical composition, drug delivery, and pharmacokinetics, with protection extending through 2043. More than 98 issued United States patents and more than 131 issued foreign patents covering the company’s AXS-07 product candidate, and related compounds, have claims covering various aspects, including pharmacokinetics, pharmaceutical composition, method of delivery, and methods of use with protection extending through 2040. Eight issued United States patents and two issued foreign patents covering the company’s AXS-12 product candidate with protection extending through 2039. The company has pending PCT applications, as well as pending applications in Australia, Brazil, Canada, Chile, China, Europe, Hong Kong, Israel, Japan, Mexico, Panama, Singapore, South Korea, and New Zealand. The company has other patent applications with claims covering the other programs in its pipeline, including those that are not relevant to its programs in development. As with respect to Sunosi, Orange Book listed patents in the United States extend out to 2042. The company also has patents in various other countries pertaining to Sunosi.
Sales and Marketing
The company has built a commercial infrastructure in the United States to commercialize its products and will further expand that team as it plans for anticipated drug approvals of its product candidates. The company has implemented a targeted sales force required to commercialize its products. Support for this team includes sales management, internal sales support, market access, distribution support, and an internal marketing group.
Research and Development
The company’s research and development expenses were $187.1 million for the year ended December 31, 2024.
Government Regulation and Product Approval
The company’s business activities, including but not limited to, research, sales, promotion, marketing, distribution, medical education, sponsorships, relationships with prescribers and other referral sources, are subject to regulation by numerous federal and state regulatory and law enforcement authorities in the United States in addition to the FDA, including potentially the Department of Justice, HHS and its various divisions, including the Centers for Medicare & Medicaid Services, or CMS, the Office of Inspector General, or OIG, and the Health Resources and Services Administration, or HRSA, the Department of Veterans Affairs, the Department of Defense, and certain state and local governments. The company’s business activities must comply with numerous healthcare laws, including but not limited to, anti-kickback and false claims laws and regulations, as well as data privacy and security laws and regulations.
The Foreign Corrupt Practices Act obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
Competition
CNS Product Candidates
AXS-05 Competition
The company is aware of other companies working to develop therapeutics for the treatment of agitation associated with AD, including Otsuka Pharmaceutical Co. Ltd., which is working to develop a combination of deuterated dextromethorphan and quinidine, and Otsuka and Lundbeck A/S, which recently received approval for Rexulti for this indication.
AXS-07 Competition
The company is aware of several companies developing compounds for migraine, including Biohaven Ltd., Kallyope, Inc., and Lundbeck A/S.
AXS-12 Competition
The company is aware of several companies developing compounds for the treatment of the symptoms of narcolepsy, including Takeda Pharmaceuticals Company, Centessa Pharmaceuticals plc, Harmony Biosciences LLC, Eisai Co., Ltd., and Alkermes plc.
AXS-14 Competition
The company is aware of other companies working to develop therapeutics for the treatment of fibromyalgia, including Dogwood Therapeutics, Inc. and Tonix Pharmaceutical Holding Corp.
History
Axsome Therapeutics, Inc. was founded in 2012. The company was incorporated under the laws of the state of Delaware in 2012.
