Dextromethorphan Hydrobromide Hydrate

据预计，到2030年，全球抗抑郁药市场将超百亿元，巨大的市场吸引药企前赴后继，而国内已上市抗抑郁药大多以进口和仿制为主。 2022年11月，首款国产自主研发的抗抑郁新药盐酸托鲁地文拉法辛缓释片获批上市，具有里程碑式意义。 除此之外，仍有很多在研的国产抑郁症新药，其中吉贝尔药业的JJH201501片于近期开展临床III期试验、上海医药集团1类新药SPH7450片也于近期获得临床试验默示许可。 国产抗抑郁新药赛道开始火热，谁将成为国产第二款抗抑郁新药？ 01 国产第二款花落谁家？ 据不完全统计，全球已上市抗抑郁品种60-70个，国内一线抗抑郁新药长期处于空白状态，直到2022年11月，绿叶制药的盐酸托鲁地文拉法辛缓释片（商品名：若欣林）获批上市，成为中国首个自主研发并拥有自主知识产权用于治疗抑郁症的化药1类创新药。 除此之外，国内有多款在研的用于治疗抑郁症的创新药，如吉贝尔药业的JJH201501、华海药业的盐酸羟哌吡酮、豪森药业的HS-10353和广为医药的GW-117等。 表1 国产在研的抑郁症新药（部分） 数据来源：公开信息整理 JJH201501是由吉贝尔研发的沃替西汀衍生物，是一种新型的多受体作用机制的抗抑郁药，目前已完成了I期、IIa期和IIb期临床研究。 临床研究表明，JJH201501可明显延长药物在人体内的半衰期，延长药物体内滞留时间，提高药物在体内的血药浓度以及AUC，减慢药物在体内的代谢速度，该品种具有显著的抗抑郁作用，与伏硫西汀比较，显示出更好的安全性，有望成为新型抗抑郁症药物（图1）。 图1 JJH201501的研发进展 图片来源：吉贝尔药业官网 目前，抗抑郁新药JJH201501正在有序开展Ⅲ期临床试验，按目前的计划，预计2025年完成Ⅲ期临床研究，申报生产批件和新药证书。 盐酸羟哌吡酮是由浙江华海药业股份有限公司和中国人民解放军军事医学科学院毒物药物研究所研发的一种小分子药物，是国内首个获批临床的SPARI类（5-HT部分激动剂和重摄取抑制剂）的1.1类化学抗抑郁药，该药靶标机制新颖明确，具有强效广谱、起效快速、兼有促认知作用、无性功能障碍等优势。 HS-10353是由豪森药业研发的新一代γ-氨基丁酸A型受体（GABAA）受体正向变构调节剂，用于治疗产后抑郁症患者，目前正在进行用于评估有效性和安全性的Ⅱ期临床试验。 BRII-296是由腾盛博药研发的一种γ-氨基丁酸A型受体阳性变构调节物，是一款针对产后抑郁的新型长效单次注射疗法，并且BRII-296口服利用度非常低，不会通过母乳影响到婴儿。 2022年9月，腾盛博药公布BRII-296的1期研究的顶线结果。研究结果表明，通过肌肉注射注射600 mg BRII-296的单次治疗实现了剂量线性、早期药物吸收、渐进和缓释曲线，无需剂量滴定或逐渐减量，从而为该剂量有可能在治疗产后抑郁方面实现临床疗效提供了信心。 02 全球新机制抗抑郁药物 全球已有多款药物上市，常用的抗抑郁症药物有灵北的艾司西酞普兰、辉瑞的舍曲林、艾伯维的氟伏沙明、GSK的帕罗西汀、礼来的度洛西汀和惠氏的艾拉法辛等。 此前，国内抗抑郁症市场主要被辉瑞、灵北、礼来3家外资药企占领，2020H1中国公立医疗机构终端抗抑郁药销售额超过43亿元，同比增长2.01%。从厂家销售格局看，辉瑞、灵北、礼来3家外资企业长期霸榜前三，市场份额分别为15.98%、8.4%、11.38%。 近几年，国外药企在抑郁症新药领域进行更深入的研究，如2022年8月，美国生物医药公司Axsome的抗抑郁口服药Auvelity获得美国FDA批准，用于治疗成年人抑郁症（MDD），是60多年来全球首个采用新机制的抗抑郁口服药，在拥挤的抗抑郁老药市场中开辟了一个新市场。 Auvelity是一款右美沙芬（45mg）+安非他酮（105mg）复方缓释片，是全球目首款口服速效NMDA（一种离子型谷氨酸）受体拮抗剂，针对包括谷氨酸在内的几种神经递质。 2023年8月4日，渤健和Sage Therapeutics公司共同开发的神经活性类固醇γ-氨基丁酸A型（GABAA）受体阳性别构调节剂Zurzuvae（Zuranolone）获FDA批准，成为首个也是唯一一个用于成人产后抑郁症（PPD）口服治疗药物。 Zuranolone是一种每日一次、为期两周的在研疗法，具有在14天快速缓解抑郁症状的潜力，与市面上大部分抑郁药物需要约6-8周才能见效相比，具有差异性。 2023年4月，强生的盐酸艾司氯胺酮鼻喷雾剂（速开朗）获得中国国家药品监督管理局上市许可批准，成为中国获批的首个具有全新作用机制和给药方式的抗抑郁药物，用于与口服抗抑郁药联合，可快速缓解伴有急性自杀意念或行为的成人抑郁症患者的抑郁症状。 由此可见，大药企正在通过开发更为快速方便给药的抗抑郁症药，因为抑郁症药物起效时间非常重要，有些重度抑郁症患者可能上午看过病，下午就自杀了，所以未来的趋势必然是更快速口服抑郁药物。 03 抑郁症药物市场巨大 抑郁症，在全球已发展为一种常见疾病，具有患病率高、自杀率高、疾病负担重等特点，是青少年的第3大疾病负担；同时，自杀也是15-29岁人群的第2大死亡原因。 据2022年《柳叶刀》一篇系统综述报道显示，全球范围抑郁症与焦虑症患病率正在上升。 研究发现，若无疫情影响，2020年全球抑郁症患病率估测为2470.5/10万，相当于全球共1.93亿人患抑郁症。但在疫情影响下，患病率上升至3152.9/10万，即全球共2.46亿人患抑郁症。疫情导致2020年抑郁症患病率增加了约0.53亿，增加幅度约27.6% 抗抑郁药市场空间庞大，根据Research and Markets报告分析，全球抗抑郁药市场预计到2030年将达176亿美元，2022-2030年复合增长率2.5%。 在国内，抑郁症市场也有巨大的上升空间，据公开的市场数据报道，2013年我国抗抑郁药市场销售额为41亿元，2018年则增长至87亿元；据相关统计，2019年中国公立医疗机构终端抗抑郁药物销售额突破90亿元；高禾投资研究中心保守估计我国潜在的抑郁症市场规模约为140亿元。 随着越来越多抑郁症案例报道，全球对抑郁症的关注日益剧增，据估计，全世界每年有5%的成年人患有抑郁症。在高收入国家，约一半的抑郁症患者未得到诊断或治疗，而在中低收入国家，这一比例则达到80-90%。 目前临床中使用的大部分抗抑郁药物作用机制是以调节单胺类递质系统为基础，即通过调控5-HT、NE、DA等递质水平来缓解抑郁症状，但这些传统的抗抑郁药存在起效慢、复发率高、缓解率低、不良反应较多和用药时间长等缺点，巨大未满足的市场需求急需更为安全有效的抗抑郁新药。 04 结语 随着人们意识的觉醒，人们对抑郁症群体越来越关注，愿意治疗的人群也越来越多，市场前景广阔，有很大的市场需求，急需更快速高效方便的抗抑郁新药。 参考文献 1.COVID-19 Mental Disorders Collaborators.Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic[published online ahead of print,2021 Oct 8].Lancet.2021;S0140-6736(21)02143-7.doi:10.1016/S0140-6736(21)02143-7 2.吉贝尔药业成功举办JJH201501片Ⅲ期临床研究全国研究者启动会 3.Brii Biosciences Announces Top-line Results from Phase 1 Study of BRII-296,A Long-Acting Therapy in Development for Postpartum Depression 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。 责任编辑 | 德清君 转载开白 | 马老师 18996384680（同微信） 商务合作 | 王存星 19922864877（同微信）  阅读原文，是受欢迎的文章哦

NEW YORK, May 28, 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 data from its industry-leading portfolio of novel products for CNS disorders will be presented at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, being held May 28-31, 2024, in Miami Beach, Florida. The presentations include new data from post-hoc analyses of Auvelity® showing improvements in anhedonic symptoms that strongly correlate with improvements in daily function in patients with major depressive disorder (MDD) and data on the clinical profile of AXS-05 in treatment of Alzheimer’s disease agitation. Details for the presentation are as follows: Major Depressive Disorder Title: Effects of AXS-05 (Dextromethorphan-Bupropion) in Improving Anhedonia and Interest-Activity Symptoms of MDD and the Associated Improvements in Functional ImpairmentPresentation Date and Time: Wednesday, May 29, 11:15 a.m. – 1 p.m.Lead Author: Roger McIntyre, MD, Professor of Psychiatry and Pharmacology at the University of TorontoPoster Number: W17Location: Salon 4 Title: Real-World AXS-05 Patient Characteristics in Major Depressive DisorderPresentation Date and Time: Wednesday, May 29, 11:15 a.m. – 1 p.m.Lead Author: Andrew Muzyk, MD, Associate Professor of the Practice of Medical Education at Duke UniversityPoster Number: W40Location: Salon 4 Alzheimer’s Disease Agitation Title: Clinical Profile of AXS-05 (Dextromethorphan-Bupropion) in Treating Alzheimer’s Disease Agitation (ADA): Results From The Phase 2/3 Development ProgramPresentation Date and Time: Wednesday, May 29, 11:15 a.m. – 1 p.m.Lead Author: Jeffrey Cummings, MD, ScD, Vice Chair of Research, UNLV Department of Brain HealthPoster Number: W47Location: Salon 4 Cognition Title: Solriamfetol Improves Cognitive Performance in Preclinical Models of Sleep Apnea and in a Randomized Placebo-controlled Study of Sleep Apnea Participants (SHARP)Presentation Date and Time: Thursday, May 30, 12:30 p.m. – 2:15 p.m.Lead Author: David Gozal, MD, MBA, Marie M. and Harry L. Smith Endowed Chair and the Chairman of the Department of Child Health at the University of Missouri Poster Number: T38Location: Salon 4 About AUVELITY®AUVELITY is a novel, oral, NMDA receptor antagonist with multimodal activity approved for the treatment of MDD in adults. AUVELITY is a proprietary extended-release oral tablet containing dextromethorphan HBr (45 mg) and bupropion HCl (105 mg). The dextromethorphan component of AUVELITY is an antagonist of the NMDA receptor (an ionotropic glutamate receptor) and a sigma-1 receptor agonist. These actions are thought to modulate glutamatergic neurotransmission. The bupropion component of AUVELITY is an aminoketone and CYP2D6 inhibitor which serves to increase and prolong the blood levels of dextromethorphan. The exact mechanism of action of Auvelity in the treatment of depression is unclear. AUVELITY received Breakthrough Therapy designation from the FDA for the treatment of MDD. INDICATION AND IMPORTANT SAFETY INFORMATION WHAT IS AUVELITY (aw-VEHL-ah-tee)? It is a prescription oral medicine used to treat adults with major depressive disorder (MDD). It is not known if Auvelity is safe and effective for use in children. Auvelity is not approved for uses other than the treatment of MDD. The ingredients in Auvelity, bupropion and dextromethorphan, are the same ingredients found in some other medicines approved for other uses. WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT AUVELITY? Auvelity and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. Auvelity is not for use in children. You should pay close attention to any new or sudden changes in mood, behavior, thoughts, or feelings or if you develop suicidal thoughts or actions. This is very important when starting or changing the dose of an antidepressant medicine. Call your healthcare provider (HCP) or get emergency help right away if you or your loved one have any of the following symptoms, especially if they are new, worse, or worry you: suicidal thoughts or actionsnew or worsening depression or anxietyagitation or restlessnesstrouble sleeping (insomnia)acting aggressive, being angry violentan extreme increase in activity and talking (mania)panic attacksnew or worsening irritabilityacting on dangerous impulsesother unusual changes in behavior or mood Do not take Auvelity if you: have or had a seizure disorder.have or had an eating disorder like anorexia or bulimia.have recently and suddenly stopped drinking alcohol or use medicines called benzodiazepines, barbiturates, or anti-seizure medicines, and you have recently suddenly stopped taking them.are taking a monoamine oxidase inhibitor (MAOI), have stopped taking an MAOI in the last 14 days, or are being treated with the antibiotic linezolid or intravenous methylene blue. Ask your HCP or pharmacist if you are unsure whether you take an MAOI. Do not start taking an MAOI until you have stopped taking Auvelity for at least 14 days.are allergic to dextromethorphan, bupropion, or any other ingredients in Auvelity. Auvelity may cause serious side effects. Ask your HCP how to recognize the serious side effects below and what to do if you think you have one: Seizures. There is a risk of seizures during treatment with Auvelity. The risk is higher if you take higher doses of Auvelity, have certain medical problems, or take Auvelity with certain other medicines. Do not take Auvelity with other medicines unless your healthcare provider tells you to. If you have a seizure during treatment with Auvelity, stop taking Auvelity and call your HCP right away. Do not take Auvelity again if you have a seizure. Increases in blood pressure (hypertension). Some people may get high blood pressure during treatment with Auvelity. Your HCP should check your blood pressure before you start taking and during treatment with Auvelity. Manic episodes. Manic episodes may happen in people with bipolar disorder who take Auvelity. Symptoms may include: greatly increased energyracing thoughtsunusually grand ideastalking more or faster than usualsevere trouble sleepingreckless behaviorexcessive happiness or irritability Unusual thoughts or behaviors. One of the ingredients in Auvelity (bupropion) can cause unusual thoughts or behaviors, including delusions (believing you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your HCP. Eye problems (angle-closure glaucoma). Auvelity may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your HCP if you have eye pain, changes in your vision, or swelling or redness in or around the eye. Dizziness. Auvelity may cause dizziness which may increase your risk for falls. Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take Auvelity with certain other medicines. Call your HCP or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms: agitationhallucinationsconfusioncomafast heartbeatblood pressure changesdizzinesssweatingflushinghigh body temperature (hyperthermia)shaking (tremors), stiff muscles, or muscle twitchingloss of coordinationseizuresnausea, vomiting, diarrhea COMMON SIDE EFFECTS The most common side effects of Auvelity include dizziness, headache, diarrhea, feeling sleepy, dry mouth, sexual function problems, and excessive sweating.These are not all the possible side effects of Auvelity. Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch. BEFORE USING Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.It is important to tell your HCP if you are taking: other medicines containing bupropion or dextromethorphanmedicines to treat depression, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressantstheophyllinecorticosteroidsoral diabetes medicines or use insulin to control your blood sugarmedicines to control appetite (anorectic)nicotine medicines to help you stop smokingstreet (illicit) drugsbenzodiazepines, sedative-hypnotic (sleep medicines), or opiates If you are unsure if you take any of these medicines, ask your HCP. They can tell you if it is safe to take Auvelity with your other medicines.Tell your HCP if you are pregnant or plan to become pregnant. Auvelity may harm your unborn baby if you take it during pregnancy. Auvelity is not recommended during pregnancy. Your HCP will prescribe another treatment for females who plan to become pregnant.One of the ingredients in Auvelity passes into your breast milk. Do not breastfeed during treatment with Auvelity and for 5 days after the final dose. Tell your HCP about all your medical conditions, including if you: have problems with your liver or kidneys.have diabetes, heart disease, or high blood pressure.have a history of seizure, stroke, eating disorder, head injury, or have a tumor in your brain or spinal cord.have a history of alcohol or drug abuse.have a history of seizure, eating disorder, or abuse alcohol or drugs.have low blood sugar, low blood sodium levels, or a history of falls.you take certain other medicines that could interact with Auvelity.have or had a condition known as bipolar disorder, a family history of bipolar disorder, suicide, or depression.have high pressure in the eye (glaucoma). Review the list below with your HCP. Auvelity may not be right for you if: you drink a lot of alcohol.you abuse prescription or street drugs.you are pregnant or plan to become pregnant.you are breastfeeding or plan to breastfeed. HOW TO TAKE Auvelity is available by prescription only.Take Auvelity exactly as instructed by your HCP.Take Auvelity 1 time a day for 3 days, then increase your dose to 2 times a day (taken at least 8 hours apart). Do not take more than 2 Auvelity tablets in 24 hours.If you miss a dose, do not take an extra dose. Wait and take your next dose at the regular time. Do not take more than 1 dose of Auvelity at a time.Do not change your dose or stop taking Auvelity without talking to your HCP.Swallow Auvelity tablets whole. Do not crush, chew, or divide the tablets.Do not give Auvelity to other people.If you take too much Auvelity call your HCP or seek medical advice promptly. LEARN MORE For more information about Auvelity, call 866-496-2976 or visit Auvelity.com.This summary provides basic information about Auvelity but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other HCP about Auvelity and how to take it. Your HCP is the best person to help you decide if Auvelity is right for you. AUV CON BS 10/2022 Please see full Prescribing Information, including Boxed Warning for suicidal thoughts and behaviors, and Medication Guide. 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. Axsome Contacts: Investors:Mark JacobsonChief Operating OfficerAxsome Therapeutics, Inc.One World Trade Center, 22nd FloorNew York, NY 10007Tel: 212-332-3243Email: mjacobson@axsome.com www.axsome.com Media:Darren OplandDirector, Corporate CommunicationsAxsome Therapeutics, Inc.One World Trade Center, 22nd FloorNew York, NY 10007Tel: 929-837-1065Email: dopland@axsome.com www.axsome.com