Asenapine Maleate

The recent approval of Rovi Pharmaceuticals Laboratories' OKEDI/RISVAN (risperidone ISM) has spiked the competition among the other pharmaceutical companies that are developing novel therapies to improve the treatment landscape. RISVAN has the potential to become a blockbuster drug. LAS VEGAS, Aug. 26, 2024 /PRNewswire/ -- Schizophrenia is a severe mental illness affecting about 1% of Americans, cognitive functions, emotional responses, decision-making, and social interaction. Onset typically occurs in late teens to early 20s for men and late 20s to early 30s for women. Currently, as per the WHO, the vast majority of schizophrenia patients around the world are not receiving mental health care. Approximately 50% of people in mental hospitals have a schizophrenia diagnosis, and only 31.3% of people with psychosis receive specialist mental health care. As per DelveInsight analysis, in 2023 the total diagnosed prevalent cases of schizophrenia in the 7MM were found to be approximately 4 million cases out of which the US accounted for nearly 1.5 million cases. It is anticipated that these numbers will rise by 2034 due to several factors, including population growth, improved diagnostic techniques, increased awareness, and reduced stigma around mental health issues prompting more individuals to seek diagnosis, and potentially, environmental stressors contributing to a higher occurrence of the disorder. Schizophrenia treatment involves a blend of medication, psychological counseling, and social support. However, nearly one-third of patients do not respond sufficiently to standard treatments. Relapses, characterized by psychotic symptoms and functional impairments, are significant. Schizophrenia treatment mainly consists of antipsychotic medications that target dopamine neurotransmitters. Second-generation medications are favored because they lower the risk of severe side effects. Long-acting injectable antipsychotics can enhance adherence and improve treatment outcomes. High-dose regimens of specific medications may be advantageous for patients with severe, treatment-resistant schizophrenia. Additionally, hospitalization and electroconvulsive therapy might be necessary for patients who do not respond to medication therapy or during severe episodes. First-generation antipsychotics like chlorpromazine, fluphenazine, haloperidol, and perphenazine are effective in treating positive symptoms such as hallucinations and delusions but do not alleviate negative symptoms or cognitive impairments. Second-generation antipsychotics, including REXULTI/RXULTI (brexpiprazole), CAPLYTA (lumateperone), LATUDA (lurasidone hydrochloride), SAPHRIS (asenapine), ABILIFY MYCITE (aripiprazole tablets with sensor), VRAYLAR/REAGILA (cariprazine), SECUADO (asenapine), INVEGA SUSTENNA/TRINZA/HAYFERA (paliperidone palmitate), ARISTADA/ARISTADA INITIO (aripiprazole lauroxil), PERSERIS (risperidone), FANAPT (iloperidone), and LYBALVI (olanzapine and samidorphan), were developed to address both positive and negative symptoms, as well as cognitive symptoms. Although these medications typically have fewer extrapyramidal side effects, they can cause weight gain, sexual dysfunction, and other metabolic disorders. Additionally, elderly patients using FGAs and SGAs are at an increased risk of developing pneumonia. Learn more about the FDA-approved schizophrenia drugs @ Drugs for Schizophrenia Treatment REXULTI (brexpiprazole) is an oral tablet available in strengths from 0.25 mg to 4 mg, containing various inactive ingredients. While its exact mechanism of action is not fully understood, it work as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at serotonin 5-HT2A receptors. REXULTI was first approved in the US in July 2015 for use in adults with MDD and schizophrenia. In January 2022, it received FDA approval for pediatric patients aged 13–17. The EMA approved it in July 2018, and Japan approved it in tablet form in January 2018 and as an oral-disintegrating dose in August 2021. Generic versions of REXULTI have now been approved, which may affect its market presence. Janssen Pharmaceutical's INVEGA SUSTENNA/INVEGA TRINZA/INVEGA HAFYERA (paliperidone palmitate) is an SGA agent that seems to act as a D2 partial agonist and a 5-HT-2A receptor antagonist. INVEGA SUSTENNA is administered monthly, INVEGA TRINZA every three months, and INVEGA HAFYERA twice yearly. Paliperidone is a benzisoxazole derivative. In the EU and Japan, INVEGA SUSTENNA is marketed as XEPLION. In the EU, INVEGA TRINZA is sold as TREVICTA, and in Japan as XEPLION TRI. INVEGA HAFYERA is a long-acting injectable treatment administered in the upper buttocks every six months, providing continuous treatment and symptom control over this period. Additionally, the recent approval of RISVAN (Risperidone ISM) has intensified the competition in the schizophrenia treatment space. Risperidone ISM is a long-acting injectable antipsychotic created and patented by ROVI for treating schizophrenia in adults. From the first injection, it delivers immediate and sustained plasma drug levels without the need for loading doses or additional oral risperidone. This approval is based on the positive outcomes of the pivotal PRISMA-3 study, which assessed the efficacy and safety of Risperidone ISM in patients with schizophrenia. The study's findings demonstrate that the two doses tested (75 mg and 100 mg administered once monthly) successfully met the predetermined primary and secondary efficacy endpoints for treating patients with moderate to severe schizophrenia symptoms. Furthermore, OKEDI (risperidone ISM) was launched in Germany, the UK, and Spain in 2022. The approval was based on the positive results of the pivotal PRISMA-3 study on the efficacy and safety of risperidone ISM in schizophrenia patients. As per the estimates by Delveinsight analysts, this drug has blockbuster potential in the schizophrenia market with medium-fast uptake. To know more about schizophrenia treatment options, visit @ New Treatment for Schizophrenia The schizophrenia market is crowded with so many companies working in the domain. Various potential therapies that are projected to enter during the forecast period include Boehringer Ingelheim's Iclepertin (BI-425809), Sumitomo Pharma/Otsuka's Ulotaront (SEP-363856), Reviva Pharmaceuticals' Brilaroxazine (RP5063), Minerva Neurosciences/Mitsubishi Tanabe Pharma's Roluperidone (MIN-101/MT-210), Karuna Therapeutics (Bristol Myers Squibb)/Royalty Pharma's KarXT (xanomeline-trospium), ACADIA Pharmaceuticals' NUPLAZID (pimavanserin), Teva Pharmaceutical/MedinCell/Royalty Pharma's Olanzapine LAI (mdc-TJK/TV-44749), Neurocrine Biosciences/Mitsubishi Tanabe Pharma's Valbenazine (NBI-98854), Lyndra Therapeutics' LYN-005 (long-acting oral risperidone), Newron Pharmaceuticals' Evenamide (NW-3509), Luye Pharma's LY03010 (ER paliperidone palmitate), and others. Discover which therapies are expected to grab major schizophrenia market share @ Schizophrenia Market Report Iclepertin (BI 425809) is an investigational drug and a glycine transporter 1 (GlyT1) inhibitor aimed at addressing the brain biology related to cognitive symptoms in schizophrenia (CIAS). Abnormalities in glutamatergic signaling downstream of neuronal NMDA receptors contribute to cognitive impairment in this condition. Enhancing NMDA receptor function could potentially improve synaptic plasticity and cognition. Glycine, an essential NMDA receptor co-agonist, is modulated by glycine transporters GlyT-1 and GlyT-2, which are located in presynaptic and astrocyte membranes. These transporters regulate glycine levels by taking it up into nerve terminals and adjacent glial cells, affecting synaptic cleft glycine concentration. By inhibiting these transporters, BI 425809 aims to increase glycine levels, thereby modulating NMDA receptor function. Administered orally, this potent and selective GlyT1 inhibitor is also under investigation for Alzheimer's disease. However, early 2020 Phase II trial results did not support its continued development for this indication, and the focus has now shifted to schizophrenia, with multiple Phase III trials currently underway. Since schizophrenia, patients frequently ignore certain symptoms, such as cognitive impairment. Therefore, if approved, BI-425809 will be the first approved pharmacotherapy for the treatment of CIAS. Ulotaront (SEP-363856), developed by Sumitomo Pharma and Otsuka Pharmaceuticals, is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity. It is a small-molecule oral agent that does not bind to dopamine D2 or serotonin 5-HT2A receptors. Sunovion discovered Ulotaront in collaboration with PsychoGenics using the in vivo phenotypic SmartCube platform and associated artificial intelligence algorithms. Ulotaront is currently in late-stage development for schizophrenia and generalized anxiety disorder (GAD) in Japan and as an adjunctive treatment for major depressive disorder, schizophrenia, and GAD in the US. Top-line results from Phase III DIAMOND 1 and DIAMOND 2 trials in schizophrenia have been released, but the Phase III DIAMOND 3 trial in the US has been halted. Sumitomo Pharma has also stopped a Phase III trial for schizophrenia in Japan and another Phase II/III trial in China, Japan, Taiwan, and the Philippines, citing business strategy reasons. Despite this, two Phase III trials are still ongoing. Recently, Otsuka and Sumitomo revised their licensing agreement, excluding SEP-4199 and SEP-378614. Under this revision, Otsuka gained exclusive rights from SMPA to develop, manufacture, and commercialize ulotaront worldwide. If Otsuka successfully develops and commercializes ulotaront, they will pay up to 30 million USD (approximately 4.5 billion yen) in milestones, along with royalties based on sales, without any upfront payment. Starting January 2024, Otsuka will cover the full cost of studies conducted by both Sumitomo Pharma Group and Otsuka, except for certain studies. KarXT (xanomeline–trospium) is an oral modulator targeting muscarinic receptors found in both the central nervous system (CNS) and various peripheral tissues. This proprietary product combines xanomeline, a novel muscarinic agonist, with trospium, an approved muscarinic antagonist, to preferentially stimulate muscarinic receptors in the CNS. As a dual M1/M4 muscarinic acetylcholine receptor agonist, KarXT aims to improve the positive, negative, and cognitive symptoms of schizophrenia. The US FDA has accepted Karuna Therapeutics' NDA for KarXT for adult schizophrenia treatment, with a PDUFA date of September 26, 2024. Additionally, KarXT is undergoing multiple Phase III trials as an adjunctive treatment with standard-of-care agents for schizophrenia and is being evaluated for psychosis treatment in Alzheimer's disease patients. Following Bristol Myers Squibb's acquisition of Karuna Therapeutics, Karuna is now a wholly-owned subsidiary of BMS. At the Annual Congress of the Schizophrenia International Research Society (SIRS) in April 2024 in Italy, BMS presented promising results from the latest interim analysis of the Phase III EMERGENT-4 open-label extension trial, showing KarXT's efficacy in reducing symptoms in adults with schizophrenia. BMS plans to continue discussions with the US FDA and will release more data from the EMERGENT program later this year. Discover more about drugs for schizophrenia in development @ Schizophrenia Clinical Trials The anticipated launch of these emerging therapies for schizophrenia are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the schizophrenia market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for schizophrenia is expected to grow from USD 2.6 billion in 2023 with a significant CAGR by 2034. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the disease. The anticipated launch of these therapies is also expected to attract new entrants to the Schizophrenia market, resulting in increased competition and innovation. DelveInsight's latest published market report titled as Schizophrenia Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the schizophrenia country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The schizophrenia market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Prevalent Cases of Schizophrenia Total Diagnosed Prevalent Cases of Schizophrenia Gender-specific Diagnosed Prevalent Cases of Schizophrenia Severity-specific Diagnosed Prevalent Cases of Schizophrenia The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM schizophrenia market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this schizophrenia market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the schizophrenia market. Also, stay abreast of the mitigating factors to improve your market position in the schizophrenia therapeutic space. Related Reports Schizophrenia Pipeline Schizophrenia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key schizophrenia companies, including Otsuka Pharmaceutical Development & Commercialization, Inc., Gedeon Richter Ltd., Lyndra Therapeutics, Neurocrine Bioscience, Takeda Pharmaceutical Company, Memory Pharmaceuticals, Hoffmann-La Roche, Neurocrine Biosciences, Boehringer Ingelheim, Meiji Seika Pharma Co., Ltd., SK Life Science, Inc., Alkermes, Inc. , Solvay Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, SyneuRx International (Taiwan) Corp, BioXcel Therapeutics Inc, Cognitive Research Corporation, Amarex Clinical Research, Forum Pharmaceuticals Inc, Amneal Pharmaceuticals, LLC, Recognify Life Sciences, Accutest Research Laboratories (I) Pvt. Ltd., Eli Lilly and Company, Johnson & Johnson Pharmaceutical Research & Development, L.L.C, Janssen, LP, Delpor, Inc., Jiangsu Hansoh Pharmaceutical, Cerevel Therapeutics, LLC, Zogenix, Inc., Luye Pharma, Reviva Pharmaceuticals, Alkermes, Inc., Karuna Therapeutics, Autifony Therapeutics, Neumora Therapeutics, Adex Therapeutics, among others. Schizophrenia Epidemiology Forecast Schizophrenia Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and schizophrenia epidemiology trends. Dementia Market Dementia Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key dementia companies, including Hoffmann-La Roche, Forest Laboratories, Inc., Janssen Pharmaceuticals, Inc., Merck and Co., Inc., Novartis, among others. Bipolar Depression Market Bipolar Depression Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key bipolar depression companies, including Intra-Cellular Therapies, Sunovion Pharmaceuticals, COMPASS Pathways, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

“新型递药系统——膜剂”专栏未经授权，不得转载基于生理药动学模型研究马来酸阿塞那平舌下膜的体内吸收机制Investigation of in vivo Absorption Mechanism of Asenapine Maleate Sublingual Film by Physiologically Based Pharmacokinetic Model陈 芳1，贾秋予2，王 兵1，相小强2，王 浩1*(1. 中国医药工业研究总院医药先进制造国家工程研究中心，上海 201203；2. 复旦大学药学院，上海 201203)摘    要采用GastroPlusTM 软件的口腔房室吸收转运(OCCAT) 模型和高级房室吸收转运(ACAT) 模型，结合马来酸阿塞那平舌下膜在Beagle 犬体内的药动学试验结果，构建并验证了马来酸阿塞那平的生理药动学(PBPK) 模型。通过参数敏感性分析，定量考察了原料药在水中的溶解度和体外溶出度(Z 因子值) 对生物利用度的影响，模拟和预测药物在体内溶出和吸收的动态过程。结果表明，阿塞那平在口腔中的吸收可见延迟和反向扩散现象；当溶解度大于6.2 mg/mL、体外溶出度符合在水中2 min 时溶出70％以上的条件时，药物吸收不受溶解度和溶出度的限制。在PBPK 模型分析和预测的基础上，可对舌下膜制备工艺中的固体分散技术进行简化。Beagle 犬体内药动学试验结果表明，工艺过程变更前后所得舌下膜的AUC0→ ∞ (P=0.869)、cmax(P=0.902) 和tmax(P=0.356) 未见显著性差异。因此，通过PBPK 模型有助于建立马来酸阿塞那平舌下膜的溶解度和体外溶出限度标准，并用于指导制剂研发及工艺过程的简化。关键词舌下膜；生理药动学模型；马来酸阿塞那平；口腔黏膜吸收以下为文章节选生理药动学(physiologically based pharmacokinetics，PBPK) 模型是一种根据生理学、解剖学和生物化学的知识模拟药物经循环系统向器官、组织转运并在组织中分布和代谢的过程，同时以物质平衡原理处理药动学数据，能够描述动物或人体血浆、组织和器官中化合物浓度- 时间曲线的整体模型[1]。近年来PBPK 建模和模拟越来越多地被应用于药物开发、制剂开发、质量风险评估和体内生物等效性虚拟评估等领域，逐渐成为建立药品关键质量属性与体内过程之间关系的有力工具[2]。马来酸阿塞那平(asenapine maleate，1) 是一种非典型抗精神病药，具有中枢神经系统抑制以及抗组胺和抗5- 羟色胺活性的作用，口服绝对生物利用度小于2％ [3]。1 原料药的水中溶解度约为3 mg/mL[4]，在水中2 min 的溶出率小于80％ [5]。国外上市了1 舌下片Saphris®，药物经舌下黏膜吸收，能避免首过效应，绝对生物利用度约35％ [6]。该产品中药物以无定型状态存在，在水中1 min 溶出率可达到80％以上。本课题组前期研究[5] 中将1 与载体材料PVP K30 制成固体分散体，使药物以无定型态存在，溶解度增加至172.1 mg/mL；再开发成舌下膜制剂，在水中2 min 时可溶出80％以上；该制品能在口腔中迅速溶解、释放、吸收，并且在Beagle 犬体内的药动学行为与市售舌下片一致。但固体分散体的制备过程耗时，还需采用有机溶剂。本研究建立了1 的PBPK 模型，通过参数敏感性分析，定量考察1 的水中溶解度和体外溶出度对其口腔吸收的影响，寻找处方筛选和工艺优化的质量目标，为简化1 舌下膜的生产工艺提供理论依据。↑长按二维码阅读全文作者简介：陈 芳(1979—)，女，研究员，博士生导师，从事速释制剂和黏膜给药制剂的研究。通信作者：王 浩(1967—)，男，研究员，博士生导师，从事新型制剂的开发和工程化研究。E-mail：wanghao99@hotmail.com文章详情欢迎登录《中国医药工业杂志》官网查看。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