Clomipramine Hydrochloride

7月24日，罗氏（Roche）宣布将收购Alnylam的RNA干扰（RNAi）平台中的一款处于临床II期开发阶段的高血压治疗候选药物zilebesiran。根据协议，Alnylam将获得3.1亿美元的预付款，并有资格获得额外的大量近期付款，包括未来几年的开发里程碑付款，以及监管和销售里程碑付款，总额可能达到28亿美元。高血压是一种常见的慢性病，是指血管内的血液压力持续升高，超过正常范围（140/90 mmHg或更高）。根据世界卫生组织的数据，全球有12.8亿30-79岁成年人患有高血压。在中国，高血压是我国患病人数最多的慢性病之一，其患病率仍呈上升趋势。2019年LANCET发表的研究显示，高血压在中国心血管死亡重要的危险因素中排首位。高血压患病人数非常庞大，约2.7亿。随着我国老龄化逐渐加重，以及高血压的诊断标准可能下调，中国高血压的患病人数可能接近5亿左右。其次，高血压的达标率低。我国高血压患者的知晓率约为50%，治疗率仅在30%左右，因此达标率非常低，在10%-15%之间。这就导致心血管疾病越来越多见，包括脑卒中、心肌梗死以及严重的靶器官损伤等，医疗负担加重。所以高血压的防治管理刻不容缓。高血压的药物治疗主要包括：1.ACE抑制剂（血管紧张素转换酶抑制剂）：这类药物能够抑制血管紧张素转换酶，从而减少血管紧张素的产生，舒张血管，降低血压。常见的ACE抑制剂包括依那普利、卡托普利等；2.利尿剂（利尿药）：这些药物有助于促使身体排出多余的钠和水，从而减少血管内的血液量，降低血压。常见的利尿剂包括氢氯噻嗪、托拉塞米等；3.钙通道阻滞剂：这些药物通过阻断细胞膜上的钙通道，使血管舒张，降低血压。常见的钙通道阻滞剂包括氨氯地平、硝苯地平等；4.ARB（血管紧张素Ⅱ受体拮抗剂）：这些药物能够阻断血管紧张素Ⅱ受体，从而减少血管收缩，降低血压。常见的ARB包括洛卡特普、缬沙坦等。5.β受体阻滞剂：这类药物能够阻断贝他受体，减慢心率，降低心脏的收缩力和输出量，从而降低血压。常见的贝他受体阻滞剂包括阿替洛尔、美托洛尔等；6.中枢性降压药：这些药物通过影响中枢神经系统，减少交感神经的活性，从而降低心率和血压。常见的中枢性降压药包括肼屈嗪、氯米帕明等。庞大的市场与未被满足的临床需求由于患者规模大加上用药周期长，高血压领域市场规模相当庞大。根据中国医药工业信息中心Pharma ONE智能药物大数据分析平台统计，2021年抗压药在中国三大终端的销售规模为565亿元，预计未来几年销售额将保持平稳。  图1: 国内抗压药销售额增长趋势及预测数据来源：Pharma ONE智能药物大数据分析平台‍中国医药工业信息中心说明：国内销售数据目前更新至2022年Q3，国内销售额为三大终端销售额其中，销售额排名第一的药物是拜尔1981年获批上市的硝苯地平，2021年国内销售总额达93.7亿人民币；紧随其后的是辉瑞1992年获批上市的氨氯地平，销售总额达54.3亿人民币。 图2：2021年中国销售额TOP 10的药品数据来源：Pharma ONE智能药物大数据分析平台‍中国医药工业信息中心虽然现有的高血压药物已经较为成熟，价格也便宜，但在增强药物依从性、药效，以及减少副作用方面还有待提高。比如，高血压市场当前的用药主要为日服，存在依从性较差的问题。因为需要每天服用，部分患者因为接受度等各种原因导致，会导致用药不及时。其次，是维持药效问题。有些患者可能吃一段时间药后发现血压控制的还不错，或者嫌麻烦，会主动停药，这会造成血压忽高忽低，反而增加心肌梗死和脑卒中的风险。最后，是副作用的问题，是药三分毒。比如说最常用的ACEI类（血管紧张素转换酶抑制剂）降压药，不少患者吃药后有干咳副作用。还有的降压药，对老年男性患者前列腺增生有好处，但服用后容易出现体位性低血压，出现跌倒的情况，这是非常危险的并发症。一年两针长效降压药Zilebesiran而据最新实验结果，Zilebesiran通过皮下注射的方式，打一针就能起效至少半年！Zilebesiran是一种特殊的小干扰RNA（siRNA）药物，它与N-乙酰半乳糖胺（N-GalNAc）配体共价结合，并经过多种化学修饰，通过皮下注射的方式进行给药。GalNAc能够与肝细胞表面特异表达的脱唾液酸糖蛋白受体高亲和地结合，从而实现精准的肝细胞递送。同时，Zilebesiran经过化学修饰，让它在肝细胞内能够稳定存在。肾素-血管紧张素-醛固酮系统（RAAS），是高血压发生发展的关键机制之一，血管紧张素原（angiotensinogen，aGT）是血管紧张素的唯一前体，也是Zilebesiran的作用目标。Zilebesiran在肝细胞内的作用是通过反义结合肝细胞中的血管紧张素原mRNA。这种作用抑制了肝细胞合成血管紧张素原的过程，从而使得血管紧张素的生成量减少。通过这种机制，Zilebesiran实现了长期稳定降压的效果。图3：Zilebesiran的作用机制Zilebesiran的1期临床试验结果发表在《新英格兰医学杂志》（NEJM）上。与安慰剂相比，zilebesiran与血清血管紧张素原（AGT）的剂量依赖性降低有关，在单次剂量≥200mg后持续6个月，在24小时内持续降压，从而实现持久的血压控制。Zilebesiran也证明了可接受的安全性，支持持续的临床开发。图4：Zilebesiran的1期临床试验相比于传统的降压药，Zilebesiran有着显著的优势。首先是它的长效性，Alnylam公司多年深耕RNA技术，目前的长效技术最长可支持一年一针，Zilebesiran注射频率为每年两次，从依从性的角度来讲，显著优于目前绝大多数口服药。有望通过提升依从性解决假耐药问题。其次它能够绕开耐药机制，针对肾素-血管紧张素系统(RAS)的降压药物，比如血管紧张素转换酶抑制剂（ACEI）和血管紧张素Ⅱ受体拮抗剂（ARB），长期使用发生RAS 逃逸现象，而siRNA 治疗几乎完全耗尽了血管紧张素原，可以防止RAS 逃逸，对RAS 抑制更有效，长期的血压控制更好。但Zilebesiran也存在其局限性。1.这项研究还只是1期临床试验，研究的样本量小，只有107名患者入组，而且观察时间短，仅有24周。且选取了高血压1-2级中年人群，同时排除了患有其他心脑血管疾病的患者。未来，在多系统疾病和老年患者中的疗效和安全性如何，也需要进一步验证。2.起效慢。Zilebesiran虽然作用时间长，但也存在起效慢的特点，一般2-3周才会起效，所以并不适合用于进展期高血压或单药治疗高血压急症。3.价格。根据一项社区多中心研究数据，高血压患者使用目前的常用降压药，仿制药每年花费为220.4 美元（人民币1579 元）原研药为472.7 美元（人民币3393 元）。参照其他siRNA 疗法，zilebesiran最终问世时会如何定价、成本是否会大幅增加，都会是影响药物可及性的关键问题。未来慢病市场的展望实际上，这并不是Alnylam在慢病治疗领域研发的第一个RNAi药物，早在2021年，由Alnylam和诺华合作开发的靶向PCKS9的RNAi药物Leqvio(inclisiran)，获FDA批准用于治疗成人原发性高胆固醇血症(杂合子家族性和非家族性)或混合型血脂异常，一年两针持续有效降脂。Inclisran目前已在70个国家获得上市批准，在中国大陆还处于3期临床阶段，有望年底获批在国内上市。为何siRNA药物能在慢病治疗领域闯出一片天呢？关键在于RNAi疗法化学修饰升级后的偶联递送技术。将载体递送升级为偶联递送，siRNA药物摆脱了庞大脂质纳米颗粒载体的束缚之后，在肝外实质性器官中的渗透能力大增，为更有效的肝外递送创造了可能。高血脂、高血压、高血糖这3大慢病都与肝脏里的代谢过程高度相关，存在用肝脏靶向siRNA药物治疗的可能性。未来可以预见RNAi疗法将在慢性病领域上有着广泛的应用前景，我们也将持续关注！年度发布2023年《全球药研新动态》《中国医院市场用药格局》（2023版）2023年《数图药讯》权威发布2021年度中国医药工业百强榜单解读中国仿制药发展报告（2022版）《2023年专利到期药品概述》医药行业专项报告中国医药中间体和原料药行业调研报告中国非甾体抗炎类原料药市场调研报告中国祛痰类原料药市场调研报告中国钙拮抗剂类原料药市场调研报告中国血管紧张素Ⅱ受体拮抗剂类原料药市场调研报告中国口服血糖调节类原料药市场调研报告中国中枢兴奋类原料药市场调研报告中国抗痛风类原料药市场调研报告中国脑血管病类原料药市场调研报告END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

DUBLIN, July 26, 2023 /PRNewswire/ -- The "Obsessive-Compulsive Disorder (OCD) Market Insights, Epidemiology, and Forecast to 2032" report has been added to ResearchAndMarkets.com's offering. Obsessive-Compulsive Disorder (OCD) Market: In-Depth Analysis and Treatment Landscape Obsessive-Compulsive Disorder (OCD) is a mental health disorder characterized by intrusive thoughts, images, or impulses causing anxiety, and repetitive behaviors aimed at reducing that anxiety. It follows a chronic course, often leading to years of suffering before seeking treatment. The DSM-5 diagnostic criteria for OCD remain largely unchanged from DSM-IV, with two specifiers added: insight and tic-related disorder. Market Overview: In 2022, there were approximately 12,082,000 total prevalent cases of OCD in the 7 major markets (7MM). Most diagnosed cases are severe, with 50% classified as severe, 35% as moderate, and 15% as mild. The United States accounted for the highest number of diagnosed cases in 2022, approximately 2,156,000 cases, and the OCD market size in the US was around USD 600 million. Treatment Landscape: Treatment for OCD involves building a therapeutic alliance, psychoeducation, and utilizing psychological and/or pharmacological approaches. Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for OCD, with drugs like sertraline, fluoxetine, and fluvoxamine being popular choices. Emerging Therapies: Troriluzole, developed by Biohaven Pharmaceuticals, is a promising drug in the OCD treatment landscape. It is a glutamate-release inhibitor and has shown encouraging results in clinical trials. If successful, troriluzole is expected to bring major changes in the OCD treatment landscape, offering safer and more effective options. Market Outlook: The total market size of OCD in the 7MM is projected to increase at a CAGR of ~5%, reaching approximately USD 1,000 million by 2032. The growth is driven by an increase in the prevalent pool of the disease and the launch of new therapies. Key Highlights: Obsessive-compulsive disorder (OCD) has been given increased attention in DSM-5, receiving its chapter. However, the diagnostic criteria for OCD in DSM-5 remain largely the same as in DSM-IV, requiring either obsessions or compulsions. The major change in the DSM-5 criteria for OCD is the addition of two specifiers for this diagnosis: insight and tic-related disorder. OCD symptoms may be present for years before treatment is sought, and those affected often suffer in silence. The disease follows a chronic waxing and waning course where 15% of patients have deterioration, and 5% have episodes with inter-episode recovery. The diagnosis of obsessive-compulsive disorder (OCD) is established by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, while the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is used for the assessment of its severity. In 2022, there were ~12,082,000 total prevalent cases of obsessive-compulsive disorder (OCD) in the 7MM. Most of the diagnosed cases of Obsessive Compulsive Disorder (OCD) are severe, with around 15%, 35%, and 50% of individuals having mild, moderate, and severe OCD, respectively. The United States accounted for the highest number of diagnosed cases of OCD in the 7MM, i.e., ~2,156,000 cases in 2022. In 2022, the market size of OCD was the highest in the US among the 7MM, accounting for approximately USD 600 million. Treatment of OCD comprises several components, starting with building a therapeutic alliance with the patient and psychoeducation. Then psychological and/or pharmacological approaches, and, for patients with treatment-resistant OCD, neuromodulation, and neurosurgery. The NICE guidelines propose CBT as the treatment of choice for OCD and body dysmorphic disorder due to the rigorous research invested into CBT for OCD and the effectiveness of treatment. The expected launch of troriluzole (Biohaven Pharmaceuticals) by 2027 is set to bring major changes in the treatment landscape of OCD, bringing in safer and more effective treatment options for OCD patients. Selective Serotonin Reuptake Inhibitors (SSRIs) are the most popular form of treatment for OCD, which works by increasing serotonin levels in the brain. Some widely used medications for the treatment of OCD are citalopram (CELEXA, CIPRAMIL), escitalopram (CIPRALEX, LEXAPRO), fluoxetine (PROZAC), fluvoxamine (FAVERIN, LUVOX), paroxetine (PAXIL, SEROXAT), sertraline (LUSTRAL, ZOLOFT). If these medications fail to work, a non-selective SRI may be prescribed. However, because it affects neurotransmitters in the brain other than just serotonin, there are more side effects, and therefore it is usually not a first-choice medication for treating OCD. The non-selective SRI most commonly used for treating OCD is clomipramine (ANAFRANIL). The generic alternatives of the approved marketed assets for OCD, such as sertraline hydrochloride, fluoxetine, fluvoxamine, clomipramine, etc., entered the market from 1996-2006. Key Topics Covered 1. Key Insights 2. Report Introduction 3. OCD Market Overview at a Glance 4. Executive Summary of Obsessive-compulsive Disorder (OCD) 5. Epidemiology and Market Methodology 6. Disease Background and Overview 7. Epidemiology and Patient Population 8. Patient Journey 9. Marketed Therapies 10. Emerging Therapies 11. OCD: The 7MM Market Analysis 12. KOL Views 13. SWOT Analysis 14. Unmet needs 15. Market Access and Reimbursement 16. Appendix For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets