Cognition

SURMOUNT-OSA Study Highlights Potential Dual-Action Benefits of Novel Therapy for Obesity ORLANDO, Fla., June 21, 2024 /PRNewswire/ -- Today, findings from the SURMOUNT-OSA, a study of tirzepatide in patients with obstructive sleep apnea (OSA) and obesity, were announced, revealing significant improvements in both sleep apnea severity and related metabolic issues. The results were presented as a Late-Breaking Symposium at the 84th Scientific Sessions of the American Diabetes Association® (ADA) in Orlando, FL, and were simultaneously published in the New England Journal of Medicine (NEJM). OSA affects up to 1 billion people globally and over 30 million adults in America alone. It is particularly common in individuals with obesity, which is the most significant risk factor. About 40% of people with obesity have OSA, and around 70% of OSA patients have obesity. This condition, marked by repeated airway obstruction during sleep, leads to various health issues, including hypertension, cardiovascular disease, diabetes, stroke, and impaired cognitive function. Traditional treatments for OSA, like continuous positive airway pressure (CPAP) devices, do not address obesity revealing a need for solutions that can treat both sleep apnea and obesity. The SURMOUNT-OSA study investigates tirzepatide, a novel treatment targeting both conditions. The two randomized, double-blind, placebo-controlled trials included 469 individuals with moderate-to-severe OSA and obesity. Study 1 enrolled patients unable or unwilling to use PAP therapy and Study 2 enrolled patients on PAP therapy at baseline. Participants were assigned to receive either tirzepatide or a placebo for 52 weeks. The primary endpoint was the change in the apnea-hypopnea index (AHI), which measures the severity of sleep apnea. Key secondary endpoints included change of sleep apnea specific hypoxic burden (SASHB), CV risk factors including changes in body weight, systolic blood pressure and inflammation (hsCRP), and changes in patient-reported sleep related impairment and sleep disturbance. Key findings revealed that participants who took tirzepatide experienced a significant decrease in AHI compared to those who took the placebo, indicating an improvement in sleep disordered breathing. In Study 1, the change in AHI at 52 weeks was -27.4 and -30.4 events/h with tirzepatide and -4.8 and -6,0 events/h with placebo in Study 1 and Study 2, respectively. Notable changes of CV risk factors included reductions in body weight (18% in Study 1, and 20% in Study 2) and improvements in systolic blood pressure (-9.6 in Study 1 and -7.6 in Study 2). "The results of the study have demonstrated the ability of tirzepatide to address both obesity and sleep apnea, offering an effective and comprehensive treatment solution," said Atul Malhotra, MD, professor of medicine at University of California San Diego School of Medicine, director of sleep medicine at UC San Diego Health, and the study's principal investigator and lead author of the NEJM article. "Its potential to be used alongside or independently of CPAP could revolutionize how we manage these interconnected conditions. These findings show the potential for the first highly effective drug treatment for sleep apnea." Looking ahead, the authors emphasized the need for further analyses to explore the long-term benefits of tirzepatide on cardiovascular outcomes and its potential role in the broader management of obesity-related conditions. Research presentation details: Dr. Malhotra will present the findings at the following symposium: Late-Breaking Symposium: SURMOUNT-OSA Trial Results and Potential Role of Tirzepatide in Treating Obesity-Related Obstructive Sleep Apnea Presented on Friday, June 21, 2024 at 3:45 PM ET. About the ADA's Scientific Sessions The ADA's 84th Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in Orlando, FL on June 21-24. More than 11,000 leading physicians, scientists, and health care professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes. Attendees will receive exclusive access to thousands of original research presentations and take part in provocative and engaging exchanges with leading diabetes experts. Join the Scientific Sessions conversation on social media using #ADAScientificSessions. About the American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For 83 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure. Through advocacy, program development, and education we aim to improve the quality of life for the over 136 million Americans living with diabetes or prediabetes. Diabetes has brought us together. What we do next will make us Connected for Life®. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (1-800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), Twitter (@AmDiabetesAssn), and Instagram (@AmDiabetesAssn). Contact: Amy Robinson [email protected] SOURCE American Diabetes Association

A new review of research evidence has explored the key differences in how women and men sleep, variations in their body clocks, and how this affects their metabolism. A new review of research evidence has explored the key differences in how women and men sleep, variations in their body clocks, and how this affects their metabolism. Published in Sleep Medicine Reviews, the paper highlights the crucial role sex plays in understanding these factors and suggests a person's biological sex should be considered when treating sleep, circadian rhythm and metabolic disorders. Differences in sleep The review found women rate their sleep quality lower than men's and report more fluctuations in their quality of sleep, corresponding to changes throughout the menstrual cycle. "Lower sleep quality is associated with anxiety and depressive disorders, which are twice as common in women as in men," says Dr Sarah L. Chellappa from the University of Southampton and senior author of the paper. "Women are also more likely than men to be diagnosed with insomnia, although the reasons are not entirely clear. Recognising and comprehending sex differences in sleep and circadian rhythms is essential for tailoring approaches and treatment strategies for sleep disorders and associated mental health conditions." The paper's authors also found women have a 25 to 50 per cent higher likelihood of developing restless legs syndrome and are up to four times as likely to develop sleep-related eating disorder, where people eat repeatedly during the night. Meanwhile, men are three times more likely to be diagnosed with obstructive sleep apnoea (OSA). OSA manifests differently in women and men, which might explain this disparity. OSA is associated with a heightened risk of heart failure in women, but not men. Sleep lab studies found women sleep more than men, spending around 8 minutes longer in non-REM (Rapid Eye Movement) sleep, where brain activity slows down. While the time we spend in NREM declines with age, this decline is more substantial in older men. Women also entered REM sleep, characterised by high levels of brain activity and vivid dreaming, earlier than men. Variations in body clocks The team of all women researchers from the University of Southampton in the UK, and Stanford University and Harvard University in the United States, found differences between the sexes are also present in our circadian rhythms. They found melatonin, a hormone that helps with the timing of circadian rhythms and sleep, is secreted earlier in women than men. Core body temperature, which is at its highest before sleep and its lowest a few hours before waking, follows a similar pattern, reaching its peak earlier in women than in men. Corresponding to these findings, other studies suggest women's intrinsic circadian periods are shorter than men's by around six minutes. Dr Renske Lok from Stanford University, who led the review, says: "While this difference may be small, it is significant. The misalignment between the central body clock and the sleep/wake cycle is approximately five times larger in women than in men. Imagine if someone's watch was consistently running six minutes faster or slower. Over the course of days, weeks, and months, this difference can lead to a noticeable misalignment between the internal clock and external cues, such as light and darkness. "Disruptions in circadian rhythms have been linked to various health problems, including sleep disorders, mood disorders and impaired cognitive function. Even minor differences in circadian periods can have significant implications for overall health and well-being." Men tend to be later chronotypes, preferring to go to bed and wake up later than women. This may lead to social jet lag, where their circadian rhythm doesn't align with social demands, like work. They also have less consistent rest-activity schedules than women on a day-to-day basis. Impact on metabolism The research team also investigated if the global increase in obesity might be partially related to people not getting enough sleep -- with 30 per cent of 30- to 64-year-olds sleeping less than six hours a night in the United States, with similar numbers in Europe. There were big differences between how women's and men's brains responded to pictures of food after sleep deprivation. Brain networks associated with cognitive (decision making) and affective (emotional) processes were twice as active in women than in men. Another study found women had a 1.5 times higher activation in the limbic region (involved in emotion processing, memory formation, and behavioural regulation) in response to images of sweet food compared to men. Despite this difference in brain activity, men tend to overeat more than women in response to sleep loss. Another study found more fragmented sleep, taking longer to get to sleep, and spending more time in bed trying to get to sleep were only associated with more hunger in men. Both women and men nightshift workers are more likely to develop type 2 diabetes, but this risk is higher in men. Sixty-six per cent of women nightshift workers experienced emotional eating and another study suggests they are around 1.5 times more likely to be overweight or obese compared to women working day shifts. The researchers also found emerging evidence on how women and men respond differently to treatments for sleep and circadian disorders. For example, weight loss was more successful in treating women with OSA than men, while women prescribed zolpidem (an insomnia medication) may require a lower dosage than men to avoid lingering sleepiness the next morning. Dr Chellappa added: "Most of sleep and circadian interventions are a newly emerging field with limited research on sex differences. As we understand more about how women and men sleep, differences in their circadian rhythms and how these affect their metabolism, we can move towards more precise and personalised healthcare which enhances the likelihood of positive outcomes." The research was funded by the Alexander Von Humboldt Foundation, the US Department of Defense and the National Institute of Health.

NEW YORK, April 21, 2023 (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 it will be presenting five abstracts at the upcoming 2023 American Academy of Neurology (AAN) Annual Meeting, being held from April 22-27 in Boston. These presentations include new data from the SHARP study, a randomized, double-blind, placebo-controlled, crossover, multicenter trial in 59 patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) and impaired cognitive function, from which positive topline results were announced in October 20221. New data from the SHARP (Solriamfetol’s Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled) study being presented at AAN include detailed secondary endpoints for the British Columbia Cognitive Complaints Inventory (BC-CCI) and the Epworth Sleepiness Scale (ESS). “The SHARP study is exciting because it overcomes treatment barriers associated with the complex relationship between cognitive impairment and OSA,” said Hans Van Dongen, Ph.D., Professor at Washington State University and first author of the SHARP study abstract. “Endpoints from the SHARP study show potential clinical benefit for patients taking solriamfetol versus placebo, suggesting it can be a robust option for the treatment of patients with EDS due to OSA. These new data, and other studies being shared at AAN, support the notion that solriamfetol performs according to label specifications and has potential to make a meaningful difference for patients with OSA and excessive daytime sleepiness.” Additional presentations at the AAN conference highlight data on the TAAR1 agonist mechanism of action of solriamfetol, data from the ongoing SURWEY real-world experience study of Sunosi, as well as data on AXS-07, Axsome’s novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for the acute treatment of migraine. Details for the upcoming AAN presentations are as follows: Title: Effects of Solriamfetol on Cognitive Function in Participants with Cognitive Impairment Associated with Excessive Daytime Sleepiness in Obstructive Sleep Apnea: Results of the SHARP Study Poster Session: P4 - Poster Session 4 Presenting Author: Eileen Leary, Ph.D., Senior Director of Clinical Development at Axsome Date/Time: Monday, April 24, 2023, from 8 a.m. – 9 a.m. ET Title: Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion Poster Session: P4 - Poster Session 4 Presenting Author: Gregory S. Parks, Ph.D., Executive Director of Medical Affairs at Axsome Date/Time: Monday, April 24, 2023, from 8 a.m. – 9 a.m. ET Title: Solriamfetol Real World Experience Study: Initiation, Titration, Safety, Effectiveness, and Experience During Follow-Up for Patients with Narcolepsy from Germany Poster Session: P4 - Poster Session 4 Presenting Author: Samantha Floam, DMD, Director of Medical Affairs at Axsome Date/Time: Monday, April 24, 2023, from 8 a.m. – 9 a.m. ET Title: Identifying Areas of Unmet Need Among People with Migraine with an Inadequate Response to Prior Acute Therapies: Results from the MOMENTUM trial Poster Session: P7 - Poster Session 7 Presenting Author: Zachariah Thomas, PharmD, MPH, Executive Director of Medical Affairs at Axsome Date/Time: Monday, April 24, 2023, from 8 a.m. – 9 a.m. ET Title: Efficacy of AXS-07 (MOSEIC™ Meloxicam and Rizatriptan) in Patients with Risk Factors for Inadequate Response to Acute Migraine Medications Poster Session: P13 - Poster Session 13 Presenting Author: Stuart J. Tepper, MD, Professor of Neurology, Geisel School of Medicine at Dartmouth Date/Time: Thursday, April 27, 2023, from 8 a.m. – 9 a.m. ET About the SHARP Trial SHARP (Solriamfetol’s Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study) was a randomized, double-blind, placebo-controlled, crossover, multicenter, trial in which 59 patients with EDS and OSA, who were experiencing cognitive impairment, were all treated with Sunosi (solriamfetol) for 2 weeks, and with placebo for 2 weeks, with the treatment periods separated by a 1 week washout. Patients were randomized in a 1:1 ratio either to treatment with Sunosi followed by placebo (sequence 1), or to treatment with placebo followed by Sunosi (sequence 2). Sunosi was administered orally once daily, starting at 75 mg per day for the first three days and 150 mg per day for the remainder of the 2-week treatment period. The primary outcome measure was the Digit Symbol Substitution Test subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS). The Digit Symbol Substitution subtest is also referred to as “Coding.” The prespecified primary endpoint was the change from baseline in cognitive function as measured by the DSST RBANS after 2 weeks of treatment (average of the 2-, 4-, 6-, and 8-hour post-dose DSST RBANS scores). Secondary endpoints included patient reported measures of cognition including the British Columbia Cognitive Complaints Inventory (BC-CCI) and the Patient Global Impression of Severity (PGI-S) for cognitive symptoms; and the Epworth Sleepiness Scale (ESS) to measure wakefulness. The secondary endpoints were analyzed in a pre-specified testing sequence. All analyses were conducted on an intent-to-treat basis. About the SUnosi Real World Experience studY (SURWEY) Study SURWEY is an ongoing retrospective chart review among physicians in Germany, prescribing solriamfetol for patients with EDS associated with narcolepsy or OSA. Physicians prescribing solriamfetol to ≥10 patients with EDS associated with narcolepsy can take part and provide data from the patients’ medical records. Eligible patients are ≥18 years old, have been diagnosed with EDS associated with narcolepsy, achieve a stable dose on solriamfetol, and complete ≥6 weeks of solriamfetol treatment. Data related to solriamfetol dosing/titration, changes in Epworth Sleepiness Scale (ESS) scores, physician and patient impression of effectiveness, and adverse events are recorded and summarized descriptively. The present analysis focuses on data from patients with narcolepsy from Germany. About Sunosi® (solriamfetol) Sunosi is a dual-acting dopamine and norepinephrine reuptake inhibitor indicated to improve wakefulness in adult patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA). Sunosi does not treat the underlying cause of OSA and Sunosi does not take the place of any device prescribed for OSA, such as a continuous positive airway pressure (CPAP) machine. It is important that you continue to use these treatments as prescribed by your healthcare provider. Sunosi received U.S. Food and Drug Administration approval on March 20, 2019 to improve wakefulness in adult patients with EDS associated with narcolepsy or OSA and was designated a Schedule IV medicine by the U.S. Drug Enforcement Agency on June 17, 2019. SK Biopharmaceuticals Co., Ltd., the discoverer of the compound, maintains rights in 12 Asian markets, including Korea, China and Japan. Sunosi has orphan drug designation for narcolepsy in the United States. Sunosi is protected by a robust patent estate with expiries out to 2040. More information about Sunosi, including Full Prescribing Information and Medication Guide, is available here. Important Safety Information Before taking SUNOSI, tell your doctor about all of your medical conditions, including if you: have heart problems, high blood pressure, kidney problems, diabetes, or high cholesterol. have had a heart attack or a stroke. have a history of mental health problems (including psychosis and bipolar disorders), or of drug or alcohol abuse or addiction. are pregnant or planning to become pregnant. It is not known if SUNOSI will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if SUNOSI passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take SUNOSI. Do not take SUNOSI if you are taking, or have stopped taking within the past 14 days, a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI). What are the possible side effects of SUNOSI? SUNOSI may cause serious side effects, including: Increased blood pressure and heart rate. SUNOSI can cause blood pressure and heart rate increases that can increase the risk of heart attack, stroke, heart failure, and death. Your doctor should check your blood pressure before, and during, treatment with SUNOSI. Your doctor may decrease your dose or tell you to stop taking SUNOSI if you develop high blood pressure that does not go away during treatment with SUNOSI. Mental (psychiatric) symptoms including anxiety, problems sleeping (insomnia), irritability, and agitation. Tell your doctor if you develop any of these symptoms. Your doctor may change your dose or tell you to stop taking SUNOSI if you develop side effects during treatment with SUNOSI. The most common side effects of SUNOSI include: headache decreased appetite problems sleeping nausea anxiety These are not all the possible side effects of SUNOSI. Call your doctor for advice about side effects. SUNOSI (solriamfetol) is available in 75 mg and 150 mg tablets and is a federally controlled substance (CIV) because it contains solriamfetol that can be a target for people who abuse prescription medicines or street drugs. Keep SUNOSI in a safe place to protect it from theft. Never give or sell your SUNOSI to anyone else because it may cause death or harm them and it is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please find full Prescribing Information here: SUN CON ISI 05/2022 About Obstructive Sleep Apnea and Excessive Daytime Sleepiness Obstructive sleep apnea, commonly referred to as sleep apnea, is a highly prevalent disease (as high as 14% in men and 5% in women) in which excessive daytime sleepiness is a major presenting complaint in many cases. Positive Airway Pressure (PAP) therapy, with its most common form being Continuous Positive Airway Pressure (CPAP), has been shown to be an effective therapy for sleep apnea that frequently results in improvement in excessive daytime sleepiness in many patients; however, not all patients tolerate CPAP therapy and among those who tolerate CPAP, usage is highly variable. Excessive daytime sleepiness may persist in people with sleep apnea despite using CPAP. About AXS-07 AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome's MoSEIC™ (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to provide rapid, enhances and consistent relief of migraine, with reduced symptom recurrence. AXS-07 is protected by a robust patent estate extending out to at least 2036. AXS-07 is 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 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. Axsome Contacts: Investors: Mark Jacobson Chief Operating Officer Axsome Therapeutics, Inc. 22 Cortlandt Street, 16th Floor New York, NY 10007 Tel: 212-332-3243 Email: mjacobson@axsome.com Media: Darren Opland Director, Corporate Communications Axsome Therapeutics, Inc. 22 Cortlandt Street, 16th Floor New York, NY 10007 Tel: 929-837-1065 Email: dopland@axsome.com References: Axsome Therapeutics SHARP Study Topline Data Press Release, October 3, 2023: