UNITED STATES
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FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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Item 8.01 Other Events.
On March 25, 2024, Axsome Therapeutics, Inc. (the “Company”) issued a press release announcing the results of its SYMPHONY Phase 3 trial of AXS-12 (reboxetine) in narcolepsy (the “SYMPHONY Trial”) and will post a presentation regarding the SYMPHONY Trial on its website.
The full text of the press release is filed as Exhibit 99.1 hereto, and a copy of the presentation is filed as Exhibit 99.2 hereto, and in each instance is incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
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99.1 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Axsome Therapeutics, Inc. |
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March 25, 2024 |
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/s/ Herriot Tabuteau, M.D. |
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Herriot Tabuteau, M.D. |
Exhibit 99.1
Axsome Therapeutics Announces AXS-12 Achieves Primary Endpoint in the SYMPHONY Phase 3 Trial in Narcolepsy
AXS-12 statistically significantly reduced cataplexy attacks compared to placebo (p=0.018, primary endpoint)
AXS-12 achieved statistically significant remission of cataplexy compared to placebo (p=0.008)
AXS-12 statistically significantly reduced excessive daytime sleepiness (EDS) severity compared to placebo (p=0.027, CGI-S for EDS)
AXS-12 statistically significantly improved concentration and memory compared to placebo (p=0.004, Cognitive Function items of FOSQ-10)
AXS-12 statistically significantly reduced overall severity of narcolepsy compared to placebo (p=0.007, CGI-S for narcolepsy)
AXS-12 statistically significantly improved overall function and quality of life compared to placebo (p=0.005, FOSQ-10 total score)
Company to host conference call and webcast today at 8:00 AM ET
NEW YORK, March 25, 2024 (Globe Newswire) – Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that AXS-12 (reboxetine), a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator, achieved the primary endpoint and significantly reduced the frequency of cataplexy attacks as compared to placebo in patients with narcolepsy in the SYMPHONY Phase 3 trial. AXS-12 also reduced excessive daytime sleepiness (EDS) severity, improved cognitive function, and reduced overall narcolepsy severity as compared to placebo. SYMPHONY was a Phase 3 multicenter, randomized, double-blind, placebo-controlled trial in which 90 patients with a diagnosis of narcolepsy with cataplexy were randomized to treatment with AXS-12 or placebo for 5 weeks.
“AXS-12 is a novel therapeutic approach to the treatment of narcolepsy as evidenced by the strong clinical results generated from the Phase 3 SYMPHONY trial, including a rapid and significant reduction in cataplexy events compared to placebo,” commented Dr. Michael Thorpy, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine. “Despite the existence of multiple approved narcolepsy treatments, significant unmet need still exists given the high rates of persistent symptoms reported by patients. Based on the concurrent improvements observed on cataplexy, severity of excessive daytime sleepiness, cognition and overall function, I believe AXS-12 represents a meaningful enhancement to the treatment armamentarium for narcolepsy patients and clinicians and will be a welcome treatment option in our fight against the devastating impact of narcolepsy on patients and their loved ones.”
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, with reductions of 83% for AXS-12 and 66% for placebo (p=0.018). AXS-12 rapidly reduced weekly cataplexy attacks, demonstrating at Week 1 a reduction of 56% compared to a reduction of 31% for placebo (p=0.007).
AXS-12 induced remission of cataplexy and increased cataplexy-free days compared to placebo. Remission of cataplexy, defined as a 100% reduction from baseline, was achieved at Week 5 by 33% of AXS-12 treated patients compared to 9.5% of placebo patients (p=0.008). Achievement of remission was rapid, being experienced at Week 2 by 24% of AXS-12 treated patients compared to 4.5% of placebo patients (p=0.008). AXS-12 increased the percentage of cataplexy-free days per week, defined as days with zero cataplexy attacks, to 84.5% at Week 5 compared to 22.6% for placebo (p=0.014).
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AXS-12 significantly reduced excessive daytime sleepiness (EDS) severity, assessed by the Clinician Global Impression of Severity (CGI-S) scale for EDS, compared to placebo at Week 5 with mean reductions of 1.8 points for AXS-12 compared to 0.9 points for placebo (p=0.027). Rapid improvement on the CGI-S for EDS was seen as early as Week 1 compared to placebo (p=0.006). AXS-12 concurrently improved EDS and cataplexy as compared to placebo. Concurrent EDS and cataplexy response was achieved at Week 5 by 57% of patients treated with AXS-12 compared to 33% of placebo patients (p=0.029). Concurrent EDS and cataplexy response was defined as a ≥30% reduction in inadvertent naps (EDS response), and a ≥50% reduction in cataplexy attacks (cataplexy response).
A decrease in the number of inadvertent naps was experienced by 54% of AXS-12 patients at Week 5 compared to 28% of placebo patients (p=0.016), assessed by the Narcolepsy Symptom Assessment Questionnaire (NSAQ). Improvement on the Epworth Sleepiness Scale (ESS) was numerically greater for AXS-12 than for placebo, with mean reductions from baseline of 4.7 points for AXS-12 compared to 3.4 points for placebo. A ≥3‑point improvement from baseline on the ESS was achieved by 60% of AXS-12 patients who had a cataplexy response.
AXS-12 significantly improved concentration and memory as measured by the Cognitive Function Items of the Functional Outcomes of Sleep Questionnaire (FOSQ-10) at Week 5 (p=0.004). AXS-12 concurrently improved cognition and cataplexy as compared to placebo. Concurrent cognitive and cataplexy response was achieved at Week 5 by 41% of patients treated with AXS-12 compared to 17% of placebo patients (p=0.016). Response was defined by an increase in days patients rated their Ability to Concentrate as very good or good (cognitive response), and a ≥50% reduction in cataplexy attacks (cataplexy response).
AXS-12 improved narcolepsy overall disease condition, and patient function and quality of life. Clinicians reported a rapid and significant reduction in overall narcolepsy severity (CGI-S for narcolepsy overall) for patients treated with AXS-12 compared to placebo at Week 5 (p=0.007), with improvements observed as early as Week 1 (p<0.001). AXS-12 demonstrated significant improvement in overall patient function and quality of life as measured by the FOSQ-10 total score as compared to placebo at Week 5 (p=0.005).
Anxiety and depression, known common narcolepsy co-morbidities, was reported by 45% of study participants at baseline, as assessed by the EuroQol (EQ-5D-5L). Improvement from baseline in the Anxiety/Depression domain of the EQ-5D-5L was achieved by 55% of patients treated with AXS-12 compared to 32% of placebo patients (p=0.146).
“The SYMPHONY Phase 3 trial results confirm the promise and potential of AXS-12 for the treatment of narcolepsy,” said Dr. Herriot Tabuteau, CEO of Axsome Therapeutics. “Treatment with AXS-12 resulted in rapid and substantial reduction of cataplexy events, the primary endpoint of the SYMPHONY trial, while evidencing improvement across a range of validated global clinical, patient-reported, quality of life, and functional outcome measures. Collectively, the data generated in SYMPHONY highlight AXS-12’s positive therapeutic impact and are consistent with the results from the previously completed positive CONCERT trial. As a next step, we look forward to completing the ongoing open label safety extension trial of AXS-12 as we work to bring this treatment to individuals living with narcolepsy.”
AXS-12 was well tolerated in the trial. The most commonly reported adverse events in the AXS-12 arm were dry mouth (n=6), nausea (n=6), and constipation (n=4), which were overall mild to moderate. The rates of discontinuation due to adverse events was low (n=1 in each of AXS-12 and placebo arms). There were no serious adverse events in the trial.
AXS-12 was granted Orphan Drug Designation for the treatment of narcolepsy in October 2018. Orphan Drug Designation is granted to promising drugs intended for the safe and effective treatment of rare diseases, defined as those affecting fewer than 200,000 people in the U.S. This designation may entitle Axsome to a period of seven years of marketing exclusivity in the U.S. upon FDA approval and a waiver of the Company’s obligation to pay the FDA application user fees for the product as required by the Prescription Drug User Fee Act. AXS-12 is covered by issued patents providing protection to at least 2039.
Axsome plans to present the detailed results of the SYMPHONY trial at upcoming scientific meetings.
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Summary of Topline Results of the SYMPHONY Trial
Effect on Cataplexy
Effect on Excessive Daytime Sleepiness (EDS)
Effect on Cognitive Function
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Effect on Narcolepsy Overall, Function and Quality of Life
Anxiety/Depression Comorbidity
Safety and Tolerability
Conference Call Information
Axsome will host a conference call and webcast today at 8:00 AM Eastern to discuss the topline SYMPHONY study results in narcolepsy. To participate in the live conference call, please dial (877) 405-1239 (toll-free domestic). The live webcast can be accessed on the "Webcasts & Presentations" page of the "Investors" section of the Company’s website at axsome.com. A replay of the webcast will be available for approximately 30 days following the live event.
About the SYMPHONY Trial
SYMPHONY (Study Evaluating a Mechanistic Approach to Treating Narcolepsy) was a Phase 3, randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of AXS-12 in patients with narcolepsy. In all, a total of 90 patients were randomized in a 1:1 ratio to treatment with AXS-12 or placebo for 5 weeks. Participants took either AXS-12 (5 mg) or placebo once daily during Week 1 followed by twice daily dosing during Weeks 2-5. The median number of cataplexy attacks at baseline was 20 and Epworth Sleep Scores were 17.8 at baseline. The prespecified primary endpoint was the change in frequency of weekly cataplexy attacks. Other symptoms of narcolepsy as well as safety and tolerability were assessed throughout the study.
About Narcolepsy
Narcolepsy is a serious and debilitating orphan neurological condition that causes dysregulation of the sleep-wake cycle and is characterized clinically by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep. Cataplexy is seen in an estimated 70% of narcolepsy patients and is a sudden reduction or loss of muscle tone while a patient is awake, typically triggered by strong emotions such as laughter, fear, anger, stress, or excitement. Narcolepsy interferes with cognitive, psychological, and social functioning, increases the risk of work- and driving-related accidents, and is associated with a 1.5-fold higher mortality rate.
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About AXS-12
AXS-12 (reboxetine) is a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator under development for the treatment of narcolepsy. AXS-12 is thought to modulate noradrenergic activity to promote maintain tone during wakefulness, and noradrenergic and cortical dopamine signaling to promote wakefulness and enhance cognition. AXS-12 has been granted U.S. Food and Drug Administration (FDA) Orphan Drug Designation for the treatment of narcolepsy. AXS-12 is covered by issued patents providing protection to at least 2039. AXS-12 is an investigational drug product not approved by the FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing and delivering novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are committed to developing products that meaningfully improve the lives of patients and provide new therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
Forward Looking Statements
Certain matters discussed in this press release are “forward-looking statements”. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the continued commercial success of our Sunosi® and Auvelity® products and the success of our efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of our ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of our current product candidates; our ability to fund additional clinical trials to continue the advancement of our product candidates; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, our product candidates, including statements regarding the timing of any NDA submission; whether issues identified by FDA in the complete response letter may impact the potential approvability of the Company’s NDA for AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to our special protocol assessment for the MOMENTUM clinical trial; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the continued commercialization of Sunosi and Auvelity and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; unforeseen circumstances or other disruptions to normal business operations arising from or related to geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.
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Axsome Contacts:
Investors:
Mark Jacobson
Chief Operating Officer
Axsome Therapeutics, Inc.
One World Trade Center, 22nd Floor
New York, NY 10007
Tel: 212-332-3243
Email: mjacobson@axsome.com
www.axsome.com
Media:
Darren Opland
Director, Corporate Communications
Axsome Therapeutics, Inc.
One World Trade Center, 22nd Floor
New York, NY 10007
Tel: 929-837-1065
Email: dopland@axsome.com
www.axsome.com
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March 25, 2024 topline data
Forward Looking Statements & Safe Harbor 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,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the continued commercial success of our Sunosi® and Auvelity® products and the success of our efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of our ongoing clinical trials, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of our current product candidates; our ability to fund additional clinical trials to continue the advancement of our product candidates; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, our product candidates; whether issues identified by FDA in the complete response letter may impact the potential approvability of the Company’s NDA for AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to our special protocol assessment for the MOMENTUM clinical trial; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the continued commercialization of Sunosi and Auvelity and for the Company’s commercial launch of its other product candidates, and the potential impact on the Company’s anticipated cash runway; unforeseen circumstances or other disruptions to normal business operations arising from or related to COVID-19; and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.. This presentation contains statements regarding the Company’s observations based upon the reported clinical data. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about the Company's industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, these projections, assumptions and estimates are necessarily subject to a high degree of uncertainty and risk. Axsome, Auvelity, Sunosi, and MoSEIC, are trademarks or registered trademarks of Axsome Therapeutics, Inc. or its affiliates. Except as with respect to Auvelity and Sunosi for their approved indications, the development products referenced herein have not been approved by the FDA.
© Axsome Therapeutics, Inc. Mark Jacobson, COO Herriot Tabuteau, M.D., CEO Summary Narcolepsy: Clinical Perspective & Implications of SYMPHONY Study Results Concluding Remarks SYMPHONY topline data Q+A Michael J. Thorpy, M.D. Dr. Thorpy & Axsome team Herriot Tabuteau, M.D., CEO Today’s Agenda
SYMPHONY Phase 3 Trial of AXS-12 in Narcolepsy Summary of Topline Results AXS-12 met the primary endpoint by demonstrating a substantial and statistically significant reduction in weekly cataplexy attacks compared to placebo (p=0.018). AXS-12 achieved statistically significant remission of cataplexy compared to placebo (p=0.008). AXS-12 statistically significantly reduced excessive daytime sleepiness (EDS) severity compared to placebo (p=0.027, CGI-S for EDS). AXS-12 statistically significantly improved concentration and memory compared to placebo (p=0.004, Cognitive Function items of FOSQ-10). AXS-12 statistically significantly reduced overall severity of narcolepsy compared to placebo (p=0.007, CGI-S for narcolepsy). AXS-12 statistically significantly improved overall function and quality of life compared to placebo (p=0.005, FOSQ-10 total score). AXS-12 was well tolerated in the trial.
Narcolepsy: Mechanism of Disease Norepinephrine is important to the control of muscle tone during wakefulness. Norepinephrine and dopamine play an important in sleep-wake regulation.1-3 Loss of orexin input decreases excitation of neurons that produce norepinephrine and dopamine1,2 Decreased norepinephrine signaling Decreased dopamine signaling Decreased norepinephrine signaling may contribute to cataplexy, excessive daytime sleepiness (EDS), and cognitive impairment1,4-7 Decreased dopamine signaling may contribute to EDS and cognitive impairment1,4 Presynaptic DA neuron Dopamine and norepinephrine dysregulation in PFC from orexin loss Disrupted NE signaling that directly and indirectly maintains muscle tone Orexin loss Orexin loss Dopamine neurons Confidential: For internal discussion and planning purposes only © Axsome Therapeutics, Inc. *Type 1 narcolepsy. Cataplexy, loss of muscle tone while awake; DA, dopamine; EDS, excessive daytime sleepiness; NE, norepinephrine; NET, norepinephrine transporter; PFC, prefrontal cortex; REM, rapid eye movement. 1. Szabo ST et al. Sleep Med Rev. 2019;43:23-36. 2. Krahn LE, Zee PC, Thorpy MJ. Adv Ther. 2022;39(1):221-243. 3. Scammell TE. N Engl J Med. 2015;373(27):2654-62. 4. Stahl SM, Grady MM. J Clin Psychiatry. 2003;64 Suppl 13:13-7. 5. Burgess CR, Peever JH. Curr Biol. 2013;23(18):1719-25. 6. Wu MF et al. Neuroscience. 1999;91(4):1389-99. 7. Bruinstroop E et al. J Comp Neurol. 2012;520(9):1985-2001. Norepinephrine Norepinephrine Dopamine Dopamine Postsynaptic neuron Presynaptic NE neuron Postsynaptic neuron NET Emotional inputs activate medial prefrontal cortex Medial prefrontal cortex Medial prefrontal cortex Amygdala Amygdala No DA transporters in PFC Decreased norepinephrine signaling NET Presynaptic NE neuron Postsynaptic neuron Norepinephrine Norepinephrine reuptake reuptake reuptake PFC NEURONS PFC NEURONS SPINAL AND CRANIAL MOTOR NEURONS SPINAL AND CRANIAL MOTOR NEURONS Cranial motor neurons Norepinephrine neurons Spinal motor neurons Excitatory input Inhibitory input Ventral tegmental area Locus coeruleus A5, A7
title and content slide Increased norepinephrine and dopamine signaling in PFC Blocking norepinephrine reuptake can reduce cataplexy AXS-12 (reboxetine) is a selective norepinephrine reuptake inhibitor and cortical dopamine modulator*1-3 Increased norepinephrine Signaling2,3 Increased dopamine signaling2,3 Inhibited norepinephrine reuptake Inhibited dopamine reuptake via NET in the PFC Confidential: For internal discussion and planning purposes only © Axsome Therapeutics, Inc. *In preclinical models. Cataplexy, loss of muscle tone while awake; DA, dopamine; EDS, excessive daytime sleepiness; PFC, prefrontal cortex; NE, norepinephrine; AXS-12 improves norepinephrine and cortical dopamine signaling in narcolepsy1-3 Presynaptic DA neuron Postsynaptic neuron Presynaptic NE neuron Postsynaptic neuron NET 1. O’Gorman C et al. Poster presented at: Associated Professional Sleep Societies Annual Meeting (SLEEP); August 2020. 2. Linnér L et al. J Pharmacol Exp Ther. 2001;297(2):540-546. 3. Stahl SM. Reboxetine. In: Prescriber’s Guide: Stahl’s Essential Psychopharmacology. Cambridge University Press; 2020:681-686. NET, norepinephrine transporter; REM, rapid eye movement. AXS-12: Mechanism of Action Dopamine neurons Cranial motor neurons Norepinephrine neurons Spinal motor neurons Ventral tegmental area Locus coeruleus A5, A7
SYMPHONY Phase 3 Study Topline Data AXS-12 (reboxetine)
Trial Design and Endpoints A Phase 3 trial to assess efficacy and safety of AXS-12 as compared to placebo in the treatment of cataplexy in narcolepsy. ESS: Epworth Sleepiness Scale; NSAQ: Narcolepsy Symptom Assessment Questionnaire; QD: once daily dosing; BID: twice daily dosing Double-blind Phase (5 weeks) Screening AXS-12 (reboxetine) 1:1 randomization Placebo Study Design: Phase 3, multicenter, randomized, double-blind, placebo-controlled trial Dosing: Week 1: AXS-12 (5 mg) or placebo QD; Weeks 2-5: AXS-12 (5 mg) or placebo BID Primary Endpoint: Change in frequency of cataplexy attacks Secondary Endpoints: Measures of other symptoms of narcolepsy Safety and tolerability Enrollment & Location: N = 90 subjects, across 60 sites in the U.S & Canada Study Duration: 4-week screening period, 5-week treatment period, 1-week safety follow up
Demographics and Baseline Characteristics EDS: Excessive Daytime Sleepiness; CGI-S: Clinical Global Impressions-Severity Characteristic AXS-12 (n = 46) Placebo (n = 44) Age (years) 36 34.2 Sex (% male) 45.7% 34.1% Time since diagnosis (years, mean) 7.9 6.3 Weekly frequency of cataplexy attacks (median) 19.3 21.6 CGI-S for EDS (mean) 5.3 5.1 ESS total score (mean) 18.3 17.3 CGI-S for narcolepsy (mean) 5.2 4.9 Use of modafinil or armodafinil (%) 32.6% 29.5% Anxiety/depression, EQ-5D-5L scale (%) 45.5% 45.0%
Cataplexy Frequency: Primary Endpoint Change in Weekly Cataplexy Attacks Change in Weekly Cataplexy Attacks Rate Ratio p=0.007 p=0.006 p=0.031 p=0.031 p=0.018 Rate Ratio is calculated as the ratio of change in the AXS-12 group divided by the ratio of change in the placebo group
Achievement of Cataplexy Remission Patients Achieving Remission (100% Reduction) in Cataplexy Attacks p=0.008 p=0.013 p=0.008
Effect on Excessive Daytime Sleepiness Improvement of EDS as Measured by CGI-S EDS: Excessive Daytime Sleepiness; CGI-S: Clinical Global Impression-Severity p=0.006 p=0.002 p=0.001 p=0.027 57% of AXS-12 patients vs. 33% of placebo achieved concurrent EDS (naps) and cataplexy response (p=0.029) at Week 5 54% of AXS-12 patients vs. 28% of placebo experienced a decrease in the number of inadvertent naps assessed by the NSAQ (p=0.016) at Week 5 A ≥3-point improvement on the ESS achieved by 60% of AXS-12 patients with a cataplexy response
Improvement in Cognitive Function FOSQ-10 Cognitive Function, Concurrent Ability to Concentrate Response p=0.016 p=0.004
Effect on Narcolepsy Overall, Function and Quality of Life Narcolepsy Overall AXS-12 treatment resulted in significant reduction in overall narcolepsy severity (CGI-S for narcolepsy overall) compared to placebo at Week 5 (p=0.007). Improvement in the CGI-S for narcolepsy overall for AXS-12 compared to placebo was observed as early as Week 1 (p<0.001). Function and Quality of Life AXS-12 demonstrated significant improvement in overall patient function and quality of life as measured by the FOSQ-10 total score as compared to placebo at Week 5 (p=0.005).
Anxiety / Depression Percentage with Improvement on EQ-5D-5L Anxiety/Depression Domain p=0.146
Safety and Tolerability GI: gastrointestinal AXS-12 was well tolerated in the trial The most commonly reported adverse events in the AXS-12 arm were dry mouth (n=6), nausea (n=6), and constipation (n=4) which were overall mild to moderate. The rates of discontinuation due to adverse events was low (n=1 in each of AXS-12 and placebo arms). There were no serious adverse events in the trial.
Dr. Michael Thorpy Albert Einstein College of Medicine NARCOLEPSY Clinical Perspective and Implications of SYMPHONY Study Results © Axsome Therapeutics, Inc.
© Axsome Therapeutics, Inc. Narcolepsy Clinical Overview 185,000 in the U.S. with narcolepsy4,5 Serious, debilitating, lifelong, neurologic disorder that disrupts the boundaries between sleep and wake states.1-3 Characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis, and disturbed nocturnal sleep Narcolepsy type 1 (NT1) is narcolepsy with cataplexy, and type 2 (NT2) is narcolepsy without cataplexy (ICDS-3 classification) 1. American Academy of Sleep Medicine. ICSD-2. Chicago, IL: 2005. 2. National Institute of Neurological Disorders and Stroke. 2011. http://www.ninds.nih.gov/disorders/narcolepsy/narcolepsy.htm. Accessed July 15, 2013. 3. España RA, Scammell TE. Sleep. 2011;34(7):845-858. 4. Acquavella J et al. 2020 J Clin Sleep Med Aug 15;16(8):1255-1263 doi: 10.5664/jcsm.8482 5. Narcolepsy Network, Narcolepsy Fast Facts, accessed Feb 21, 2024 6. Barker EC, et al. 2020 Nat. Sci. Sleep; 12: 453-466 doi: 10.2147/NSS.S162762 7. Swick TJ Nat Sci Sleep. 2015; 7: 159–169. doi: 10.2147/NSS.S92140 8. Rosenberg R and Thorpy, MJ, et al. J of Clinical Sleep Medicine, Published Online, January 13, 2024; https://doi.org/10.5664/jcsm.11014 86% Cognitive impairment or brain fog8 70% Have cataplexy7 50% undiagnosed6
Narcolepsy is associated with significant morbidity, mortality, and healthcare utilization Mortality rate3 Motor vehicle accident injuries2 Hospital and physician visits1 Medication use1 Healthcare use and costs1 People with narcolepsy have: Narcolepsy leads to impaired psychosocial development, education, and employment, and often results in permanent disability and increased mortality4 1. Black J, et al. Sleep Med. 2014;15:522-529. 2. Tzeng NS et al J Clin Speep Med 2019 Jun 15; 15(6):818-889 3. Ohayon MM et al. Sleep. 2014 Mar 1; 37(3):439-444 4. Thorpy MJ and G Hiller; The Medical and Economic Burden of Narcolepsy: Implications for Managed Care. American Health & Drug Benefits; Vol 10, No 5 l July 2017
Cataplexy poses significant patient burden Results from CRESCENDO survey of treated patients1 1. CRESCENDO Survey, Axsome data on file Sudden and transient loss or reduction of muscle tone while awake, typically triggered by strong emotions (e.g., laughter, elation, surprise, anger) 77% of patients on current treatments continue to experience cataplexy1
Narcolepsy current treatment landscape Current Treatment Types Used by NT1 Patients (n=203)* Results from CRESCENDO survey of treated patients1 Currently Take Wake Promoting Agents* 53% Oxybates* 47% Stimulants* 42% Antidepressants (for narcolepsy)* 38% Other (nighttime medication)* 10% Other (daytime medication)* 7% 1. CRESCENDO Survey, Axsome data on file * Wake Promoting Agents include: modafinil, armodafinil, solriamfetol, pitolisant; Oxybates include: sodium oxybate and mixed salt oxybate; Stimulants include: methylphenidate, amphetamines, others; Antidepressants include: SSRIs, SNRIs, NDRI, tricyclics; Other nighttime medications include: zolpidem, trazodone, pramipexole and others; Other daytime medicatoins include: lamotrigine, triamterine, levothyroxine and others 37% of respondents diagnosed with depression, of whom 80% take medication to manage it.
High rates of symptoms despite current treatments Percentage of Patients With Persistent Symptoms While on Treatment* Results from CRESCENDO survey of treated patients1 Narcolepsy patients have significant pre- and post-treatment unmet needs 1. CRESCENDO Survey, Axsome data on file * Excessive daytime sleepiness (EDS) quantified using the Epworth Sleepiness Scale (ESS), with scores >10 indicating EDS; Cognitive impairment quantified using the British Columbia Cognitive Complaints Inventory (BC-CCI), with scores > 4 indicating at least mild cognitive impairment; Cataplexy and disrupted nighttime sleep are patient self-reported symptoms 77% Cataplexy 74% Cognitive Impairment 77% Disrupted nighttime sleep 64% Excessive daytime sleepiness ESS > 10 BC-CCI > 4
Implications of SYMPHONY Study AXS-12 treatment was associated with a rapid and robust efficacy on cataplexy compared to placebo, demonstrating a significant reduction in weekly attacks, achievement remission and cataplexy-free days. AXS-12 improved EDS severity as measured by the CGI-S, which was supported by patient reported improvement in advertent naps on the NAS-Q, and positive trends on the ESS. AXS-12 improved cognitive function as measured by the Cognitive Function items of the FOSQ-10, which was supported by improvement in the ability to concentrate. AXS-12 significantly reduced the severity of narcolepsy overall as measured by the CGI-S, and significantly improved quality of life and function as measured by the FOSQ-10. Depression and anxiety are known narcolepsy comorbitities; the mechanisms of action of AXS-12 may be relevant for these conditions. AXS-12 demonstrated a favorable safety and tolerability profile. Based on these results, AXS-12 would represent an important new treatment option for physicians and patients in the fight against narcolepsy
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March 25, 2024 topline data