Bushu Pharmaceuticals Ltd.

CKD-aP临床表现慢性肾脏病相关性瘙痒（Chronic Kidney Disease-Associated Pruritus, CKD-aP）或尿毒症性瘙痒是晚期或终末期肾病患者的常见且令人困扰的症状。CKD-aP主要累及面部、胸部和四肢，通常表现为大面积对称的皮肤发红区域，通常在夜间发作。与皮肤性瘙痒相比，CKD-aP患者未观察到原发性皮肤病变。脓疱、线性结皮、丘疹、溃疡和较少见的结节性痒疹的擦伤一般被视为由于强烈的抓挠活动而引起的继发性皮肤变化。一旦发展为CKD-aP，症状大多将持续数月至数年。慢性肾病相关瘙痒症（CKD-aP）患者的典型皮肤变化来源：10.1038/ki.2013.454CKD-ap的患病率慢性肾脏病的发病率逐年增高，据估计，全球肾脏病患者已达8.5亿人，我国全年龄段的CKD患者数估计已达1.2亿。美国登记的接受透析治疗的终末期肾病患者超过50万人，截至2021年底中国大陆地区登记血液透析患者近75万人。CKD-aP影响大量血液透析患者，约60%接受血液透析治疗的终末期肾病患者出现皮肤瘙痒的症状，其中的40%患者报告中度至重度瘙痒。尽管在过去几十年中，瘙痒的患病率有所下降，但这种症状仍然是透析患者中的一个主要临床症状。CKD-ap患病率来源：Cara TherapeuticsCKD-aP的发病机制CKD-aP的发病机制仍不明确，被认为是由多种因素共同引起的，包括免疫系统功能障碍、毒素积聚、代谢异常、全身炎症和内源性阿片类药物水平改变。具体来说，原因可能有：1）透析不足，无法完全清除毒素和废物；2）血液中甲状旁腺激素（PTH）水平高；3）血液中钙和磷水平过高；4）血液中镁或铝水平过高；5）体内细胞释放组胺和其他引起瘙痒的化学物质；6）汗腺萎缩导致皮肤干燥；7）慢性肾病和ESKD引起的神经损伤等。 CKD-aP潜在致病因素来源：10.1038/ki.2013.454CKD-aP的治疗方法所有CKD-aP患者均应根据Kt/V指标进行透析。Kt/V是反应透析充分性的指标，其中K代表透析设备对血浆尿素的清除率，T代表透析的时间，V代表尿素分布的容积）。如果瘙痒持续存在，可考虑尝试增加透析次数。Kt/V指标为1.5-1.7，持续1-2个月。应控制与CKD无关和相关的合并症（例如甲状旁腺功能亢进症）。应建议所有患者使用高含水量润肤剂，建议在润肤剂中添加普莫辛以加大缓解强度。局部治疗应为轻度和/或局部性CKD-aP的一线治疗。对于全身性、中至重度和/或难治性CKD-aP，应进行全身性治疗。到目前为止，加巴喷丁类药物（加巴喷丁和普瑞巴林，超适应症使用）在这些患者中具有支持其安全性和有效性的证据最多，因此被认为是一线药物，但用药剂量需要谨慎确定。随着最近的FDA批准，选择性KOR激动剂Difelikefalin可能被认为是加巴喷丁类药物的安全有效的替代品。替代和辅助治疗，如补充脂肪酸、光疗、活性炭、大麻素和针灸/穴位按压，应根据可及性、实用性、财务状况和其他合并症，逐个患者考虑。一项在欧洲进行的调查中，43%的CKD-ap患者表示他们没有特定的治疗方法选择，近四分之三（72%）的人同意CKD-aP的治疗选择有限。受访者认为在提高降低瘙痒强度的疗效（62%）和改善患者生活质量的能力（57%）方面，需要重大的治疗改进。目前国内没有获得批准的治疗方案，现有药物多为超适应症使用，例如抗组胺药和皮质类固醇等。目前的治疗方案无法提供一致的、充分的缓解，临床未满足的需求较大。CKD-ap上市药物Korsuva包装Korsuva（Difelikefalin）是唯一被FDA批准的用于治疗CKD-aP的药物，它通过选择性地靶向外周κ-阿片受体来缓解瘙痒。Korsuva通过优先审查程序获得批准，此前FDA也授予治疗CKD-ap的突破性药物资格。该上市批准基于2项关键III期临床试验的积极数据，包括在美国开展的KALM-1试验和全球性KALM-2试验，以及来自额外32项临床研究的支持性数据。伴有中度至重度CKD-aP的血液透析患者在接受Korsuva注射液治疗后，瘙痒强度和生活质量指标均表现出统计学意义的显著改善。支持获批的两个临床试验：KALM 1&KALM 2来源：cara therapeutics2022年4月KORSUVA注射液开始商业化，2022年第二季度产生了1680万美元的净销售额，2022年第三季度的净销售额为1620万美元。批发商向透析中心的发货量从第二季度的1812瓶增加到第三季度的184440瓶。Remitch包装盐酸纳呋拉啡（Remitch，TRK-820）是Toray开发的高选择性к(kappa)-opioid受体激动剂。TRK-820的软胶囊剂型于2009年起在日本上市，用于治疗血液透析相关尿毒症瘙痒。口腔崩解片于2017年在日本获批并进入市场。口腔崩解片可水服或干服，特别适用于吞咽功能受损的患者或饮水量受到限制的患者，因此预期将会提高患者的用药依从性。Remitch日本市场销售额6亿人民币（2020年，日本病人30万）。2018年1月，Toray Industries, Inc.授予三生制药在中华人民共和国大陆地区（不包括香港、澳门及台湾）开发及商业化TRK-820口腔崩解片制剂配方的独家权利。东丽株式会社/武州制药株式会社川越工厂/沈阳三生制药有限责任公司联合在中国开展临床试验验证盐酸纳呋拉啡口腔崩解片的安全性和有效性。5μg组、2.5μg组主要疗效指标均桥接成功，与日本III期试验结果一致性结论成立，这可能是国内第一款有望上市的针对血液透析患者瘙痒的药物。CKD-ap临床阶段药物目前处于临床阶段的药物有以下五款：HSK21542是由公司自主研发的、具有完全自主知识产权的强效外周Kappa阿片受体激动剂，目前针对CKD-ap的开发处于临床III期阶段。Kappa阿片受体（KOR）是经典的阿片受体之一，是一种抑制性G蛋白偶联受体（GPCR），分布在中枢神经系统（CNS）和外周组织中。由于KOR的广泛分布和相关生理功能，它已被用于探索作为许多疾病药物开发的潜在靶标，包括疼痛，炎症，瘙痒和成瘾。HSK21542不易透过血脑屏障，在发挥外周作用的同时，能避免中枢阿片类药物相关副作用，如成瘾、致幻、呼吸抑制等。体外实验结果表明，HSK21542对KOR的激动效力高于difelikefalin，脑/血浆浓度比为0.001，表明其外周选择性。在疼痛动物模型中，HSK21542显着抑制乙酸、后爪切口或慢性收缩损伤诱导的疼痛相关行为，并且在给药后15分钟与difelikefalin的疗效相当。尼莫利珠单抗是一种针对IL-31受体α的同类首个人源化单克隆抗体，可阻断来自 IL-31 的信号传导，目前针对CKD-ap的开发处于临床II/III期阶段。IL-31在直接刺激与瘙痒相关的感觉神经元并导致炎症和屏障功能障碍方面具有独特的作用，IL-31是免疫系统和神经系统之间的桥梁，同时也可以直接作用于皮肤中的结构细胞。2022年3月28日，尼莫利珠单抗在日本获得批准用于治疗特应性皮炎相关的瘙痒。nemolizumab最初由Chugai Pharmaceutical开发，现在Maruho拥有日本权益，高德美（Galderma）拥有除日本和中国台湾省之外的权益。MC2-25乳膏的活性成分是一种二肽，由MC2 Therapeutics的专有配方和药物输送系统-PAD技术™配制而成，目前针对CKD-ap的开发处于临床2期阶段。MC2-25乳膏是一种有效的异氰酸酯清除剂，可抑制>90%的蛋白质氨基甲酰化，并抵消氨基甲酰化引起的皮肤形态变化。异氰酸酯是一种非常活泼的分子，已知具有神经毒性，并且容易与体内和皮肤中存在的蛋白质、肽和氨基酸发生反应。在CKD患者中，氨基酸和蛋白质的氨基甲酰化显著上调，被认为是CKD-aP根本原因的关键因素。KL280006注射液为科伦药业研发的具有自主知识产权的选择性外周κ阿片受体激动剂，具有新颖的短肽结构，作用机制和化学结构明确，目前针对CKD-ap的开发处于临床2期阶段。KL280006注射液对外周KOR具有高亲和性和高选择性，具有显著的抗瘙痒效果，且不易透过血脑屏障，故可避免传统中枢阿片类药物的常见不良反应，如呼吸抑制、药物成瘾、便秘等，兼具良好的有效性和安全性。SHR0410是恒瑞自主研发的一款选择性κ阿片受体激动剂，针对术后疼痛的研发已经进入III期临床，目前针对CKD-ap的开发处于临床I期阶段。小结-CKD-aP透析患者中的一个主要临床症状，约60%接受血液透析治疗的终末期肾病患者出现皮肤瘙痒的症状；-国内外获批针对CKD-ap的治疗方案有限，存在超适应症使用现象。目前的治疗方法无法提供一致的、充分的缓解，临床未满足的需求较大；-目前处于临床开发阶段的CKD-ap药物有5款，作用机制包括κ阿片受体激动剂、IL-31抗体及异氰酸酯清除剂，给药方式分别为静脉注射、皮下注射和局部涂抹；-国内方面沈阳三生制药、海思科、科伦博泰、恒瑞有布局管线，均为κ阿片受体激动剂。参考来源Lipman ZM, Paramasivam V, Yosipovitch G, Germain MJ. Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches. Clin Kidney J. 2021 Oct 14;14(Suppl 3):i16-i22. doi: 10.1093/ckj/sfab167Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015 Apr;87(4):685-91. doi: 10.1038/ki.2013.454Lipman ZM, Paramasivam V, Yosipovitch G, Germain MJ. Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches. Clin Kidney J. 2021 Oct 14;14(Suppl 3):i16-i22. doi: 10.1093/ckj/sfab167EMJ Nephrol. 2021;9Supplement 3:2-11https://xueqiu.com/6883758294/193108885Wang X, Gou X, Yu X, Bai D, Tan B, Cao P, Qian M, Zheng X, Wang H, Tang P, Zhang C, Ye F, Ni J. Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch. Front Pharmacol. 2021 Nov 16;12:773204. doi: 10.3389/fphar.2021.773204👇关注药渡数据媒体矩阵

DUBLIN, Dec. 19, 2022 /PRNewswire/ -- The "Cytotoxic Drugs and HPAPI Manufacturing Market by Type of Product, Company Size, Scale of Operation, Type of Molecule, Type of Highly Potent Finished Dosage Form, and Key Geographies, Europe, Asia-Pacific and Rest of the World: Industry Trends and Global Forecasts, 2022-2035" report has been added to ResearchAndMarkets.com's offering. "Cytotoxic Drugs and HPAPI Manufacturing Market 2022-2035" report features an extensive study of the current market landscape and future potential of the HPAPI and cytotoxic drug manufacturing market, over the next decade. The study also features an in-depth analysis, highlighting the capabilities of various industry stakeholders engaged in this field. Aided by the ongoing advancements in clinical pharmacology and oncology research, as well as the rising demand for targeted therapies, high potency active pharmaceutical ingredients (HPAPIs) and cytotoxic drugs have emerged as one of the key areas of interest for researchers and drug developers worldwide. One of the key objectives of the report was to evaluate the current opportunity and the future growth potential of the HPAPI and cytotoxic drug manufacturing market over the coming years. We have provided an informed estimate on the likely evolution of the market in the short to mid-term and long term, for the period 2022-2035. The report also features a likely distribution of the current and forecasted opportunity across important parameters. In order to account for future uncertainties and to add robustness to our model, we have provided three market forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry's growth. Frequently Asked Questions What are the current opportunities within the HPAPI and cytotoxic drug market? The cytotoxic drugs and HPAPI manufacturing market is presently considered as one of the most powerful and dynamic sectors of the pharmaceutical industry. At present, more than 40% of the total number of drugs are highly potent in nature. Further, around 60% of the HPAPIs are being developed against oncological indications. Considering the upsurge in demand for novel anti-cancer therapeutics, including antibody-drug conjugates (ADCs), high potency compounds have generated significant interest among several researchers and industry stakeholders. What is the need for contract manufacturing organizations (CMOs) in the HPAPI and cytotoxic drug domain? The manufacturing of highly potent APIs and cytotoxic drugs requires an adequate working environment (to prevent cross contamination within multi-product assets), stringent manufacturing protocols (to comply with the established regulatory standards) and a trained workforce (to satisfactorily handle highly potent materials). In addition, it requires an expensive infrastructure, which is often complex to engineer, install and maintain. As a result, various companies rely on third party service providers to leverage their technologies for manufacturing highly potent and cytotoxic compounds and achieve greater operational flexibility. The inherent expertise of CMOs is believed to be capable of enabling reduction in the time-to-market a product and offer significant cost-benefits. What is the current market landscape and recent trends in the HPAPI and cytotoxic drug contract manufacturing domain? Presently, close to 145 companies have the required capabilities to offer HPAPI and cytotoxic drug manufacturing services across different scales of operation. In addition, several contract service providers are entering into strategic alliances in order to consolidate their presence in this field and enhance their existing capabilities to meet the growing demand for high potency molecules. It is worth mentioning that close to 50% of the expansion activities carried out in this market have been focused on improving the existing manufacturing facilities for highly potent molecules, through the addition of new structures and equipment. What are the key challenges faced by HPAPI and cytotoxic drug CMOs? The primary challenge faced during the manufacturing of highly potent APIs and cytotoxic drugs is related to limiting / altogether preventing cross-contamination of the highly potent molecule with other molecules being produced at the same site. Further, the lack of information related to safe exposure levels and toxicity of new chemical entities can risk the lives of workers and harm the environment. As a result, comprehensive management systems are required for safe handling and containment of highly potent molecules. In addition, proper cleaning techniques and waste treatment systems are extremely essential while producing such compounds. What are the key value drivers in the HPAPIs and cytotoxic drugs contract manufacturing market? The increasing demand for cytotoxic drugs has led to a rise in the number of HPAPIs in the overall pharmaceutical development pipeline. In order to cater to the growing demand for the production of such drug candidates, there is a requirement for safe manufacturing and containment technologies. Even though some pharmaceutical companies have made considerable investments to establish in-house capabilities, the capital-intensive nature and specialized containment requirements make the role of contract manufacturers crucial, specifically for small and mid-sized players. How is the revenue generation potential associated with cytotoxic drugs and HPAPI manufacturing market likely to evolve in the coming years? The cytotoxic drugs and HPAPI manufacturing market is projected to grow at a CAGR of approximately 12% in the coming years. Currently, in terms of type of molecule, the market is likely to be driven by highly potent small molecules. However, this trend is expected to change in the foreseen future, as the demand for highly potent biologics, such as cell and gene therapies, increases further. In addition, in terms of scale of operation, majority share of the contract service revenues is expected to be generated by commercial scale manufacturing operations. Specifically, in terms of geography, the cytotoxic drugs and HPAPI manufacturing market in Asia-Pacific is likely to grow at a relatively faster pace (~13%), in the long term. The report features detailed transcripts of interviews held with the following individuals: Antonella Mancuso and Maria Elena Guadagno (Vice President and Chief Operating Officer and Business Director, BSP Pharmaceuticals) Stacy McDonald and Jennifer L. Mitcham (Ex-Group Product Manager and Ex-Director-Business Development); Abul Khair (Business Development Associate, Catalent) Roberto Margarita (Business Development Director, CordenPharma) Klaus Hellerbrand (Managing Director, ProJect Pharmaceutics) Kevin Rosenthal (Ex-Business Head, Formulations and Finished Products, Alphora research) Mark Wright (Ex-Site Head, Grangemouth, Piramal Healthcare) Allison Vavala (Ex-Senior Manager, Business Development, Helsinn) Valentino Mandelli (Marketing and Sales Manager, Pharma, Cerbios-Pharma) Javier E. Aznarez Araiz (Ex-Business Development, Idifarma) COMPANY COMPETITIVENESS ANALYSIS HPAPI Contract Manufacturers: Company Competitiveness Analysis Highly Potent FDF Contract Manufacturers: Company Competitiveness Analysis HPAPI and Highly Potent FDF Contract Manufacturers: Company Competitiveness Analysis COMPANY PROFILES: HPAPI AND CYTOTOXIC DRUG MANUFACTURERS IN NORTH AMERICA AbbVie Cambrex Catalent Pfizer CentreOne Piramal Pharma Solutions COMPANY PROFILES: HPAPI AND CYTOTOXIC DRUG MANUFACTURERS IN EUROPE Abzena Aenova CARBOGEN AMCIS Hovione Lonza COMPANY PROFILES: HPAPI AND CYTOTOXIC DRUG MANUFACTURERS IN ASIA-PACIFIC AND REST OF THE WORLD Intas Pharmaceuticals Scinopharm STA Pharmaceutical (a WuXi AppTec company) Syngene Teva API LIST OF COMPANIES AND ORGANIZATIONS AbbVie Abzena ACES Pharma Adare Pharma Solutions ADC Biotechnology ADC Therapeutics ADIENNE Pharma and Biotech Aenova AGC Pharma Chemicals (A subsidiary of AGC Group) Agno Pharma AIMEDBIO Ajinomoto Bio-Pharma Services ALB Technology Alcami Alkermes Almac Alphora Research Altasciences Alvogen Amneal Pharmaceuticals AMPAC Fine Chemicals (A SK pharmteco company) Angelini Fine Chemicals (A subsidiary of Angelini Pharma) ANI Pharmaceuticals Antengene ANVI Pharma Aptuit (An Evotec company) Ardena Arevipharma (Acquired by Yonsung Group) Aspen API Astellas Pharma Astorg AstraZeneca Asymchem Laboratories Aurigene Pharmaceutical Services Avra Laboratories (Acquired by Advent International) Baxter BioPharma Solutions Bio-Synthesis BioTechnique BioVectra BiVictriX Therapeutics BOC Sciences Boehringer Ingelheim Bolt Biotherapeutics Boryung Pharmaceutical Bright Peak Therapeutics Bristol Myers Squibb BrYet Health Bryllan BSP Pharmaceuticals Bushu Pharmaceuticals Byondis Cambrex Capsugel (A Lonza company) CARBOGEN AMCIS (A Dishman Carbogen Amcis Group company) Catalent CellMosaic Celon Laboratories Cerbios-Pharma ChemCon ChemPartner CordenPharma CoreRx Creative Biolabs CritiTech Curia Custom Pharmaceutical Services (A part of Dr. Reddy's Laboratories) Cytopharma Daiichi Sankyo Dalton Pharma Services Dipharma Divi's Laboratories DOTTIKON EXCLUSIVE SYNTHESIS EirGen Pharma (Acquired by OPKO Health) Eisai Eli Lilly Enteris BioPharma (A subsidiary of SWK Holdings) Esteve Eurofins Scientific EVER Pharma Excella (Acquired by Fareva) Exelixis Fabbrica Italiana Sintetici Fareva Farmabios (A PharmaZell Group company) Farmhispania Femtogenix Fermion (A subsidiary of Orion) Flamma Formex (A subsidiary of Biotech Investment Group (BIG)) Formosa Laboratories Fresenius Kabi Frontida BioPharm (Acquired by Adare Pharma Solutions) Fujimoto Chemicals GeneQuantum Healthcare Genmab GENTEC PHARMACEUTICAL GROUP Gilead Sciences Glycotope Goodwin Biotechnology GP Pharm GTP Bioways Gustave Roussy Helsinn Advanced Synthesis Heraeus Hovione ICROM Idifarma (Acquired by Ardena) IDT Australia Iksuda Therapeutics ImmunoGen Indena Ind-Swift Laboratories Intas Pharmaceuticals Janssen Biotech Kodiak Sciences Kohlberg Kyongbo Pharmaceutical (A subsidiary of Chong Kun Dang Pharmaceutical) LakePharma Laurus Synthesis LegoChem Biosciences Levena Biopharma (A subsidiary of Sorrento Therapeutics) Lonza Lotus Pharmaceuticals Lubrizol Life Science MabPlex Mac-Chem (A NMS Group Company) Magle Chemoswed Malladi Drugs & Pharmaceuticals Mayne Pharma McSAF MEDICHEM Merck Mersana Therapeutics Metrics Contract Services MilliporeSigma Minafin Minakem (A subsidiary of Minafin) Mitsubishi Tanabe Pharma Mubadala MuseChem Natco Pharma Navrogen NBE-Therapeutics NerPharMa NJ Bio Normon Novartis Novasep Oasmia Pharmaceutical OEP Pharma Olon Oncotec Pharma Produktion Oxford BioTherapeutics Parabolic Drugs Patheon (Acquired by Thermo Fischer Scientific) PCI Pharma Services Pensatech Pharma Pfanstiehl Pfizer Pfizer CentreOne Pharmacare Premium Pharmaceutics International Pharmascience PharmaZell PILA PHARMA Piramal Pharma Solutions PrasFarma Procos (A subsidiary of CBC) ProJect Pharmaceutics Pyxis Oncology Quadira 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PictureDesignSwiss / Shutterstock Full data presented Tuesday afternoon from the Phase III Clarity AD trial show Eisai and Biogen's lecanemab has a favorable safety pro patients with Alzheimer's disease. The presentation at the 2022 Clinical Trials on Alzheimer's Disease (CTAD) conference comes amid mounting concerns about lecanemab's safety. In October, an unnamed Clarity AD investigator linked a patient's death to lecanemab. Now, a second death reported Monday is also being attributed to the investigational drug by an external expert. Both deaths were due to bleeding in the brain. During the CTAD session, Marwan Sabbagh, M.D., a behavioral neurologist at the Barrow Neurological Institute, said that in the randomized, placebo-controlled analysis, "there were no ARIA-related deaths." ARIA, or amyloid-related imaging abnormalities, are physiological anomalies in the brain detected by magnetic resonance imaging, often attributed to amyloid-modifying therapies. Causes of death in the lecanemab arm included cerebrovascular accident, myocardial infarction, respiratory failure, metastases to meninges and COVID-19. Nevertheless, Sabbagh conceded that two deaths were associated with cerebral microhemorrhages in the open-label extension phase of the study. One of these deaths occurred in the context of a tissue plasminogen activator, which Sabbagh said is thrombolytic with a known potential complication risk of hemorrhage. The second patient who died was on medication for atrial fibrillation, had had pneumonia and previously experienced many falls. "These cases show that the causality with lecanemab is a little difficult" to establish, Sabbagh said. Whether treatment with the investigational antibody and deaths are indeed causally related remains under investigation. ARIA suggestive of edema (ARIA-E) occurred in 12.6% of lecanemab-treated patients, as opposed to only 1.7% of the placebo arm. Nevertheless, most ARIA-E events were mild-to-moderate in severity, with 78% of such episodes being asymptomatic. Twenty-five lecanemab recipients had symptomatic ARIA-E, which typically manifested as confusion, headache and visual disturbances. Most ARIA-E episodes occurred within six months of treatment and generally resolved within four months of detection. "We know when the ARIA-E events are likely to occur and when they are likely to resolve," Sabbagh said. Questions About Clinical Meaningfulness Remain Tuesday's presentation follows an earlier efficacy readout in September, which showed lecanemab was indeed effective at slowing cognitive decline in Alzheimer's disease patients. These data, confirmed at CTAD, indicate that lecanemab slowed clinical decline by 27% as compared with placebo, as measured by the Clinical Dementia Rating scale Sum of Boxes (CDR-SB). Lecanemab also outperformed placebo on all key secondary endpoints. For instance, at 18 months, the drug candidate slowed cognitive decline by 26%, as measured by the ADAS-Cog14 scale, and disease progression by 24%, as assessed by the ADCOMS tool. Biomarker analysis also revealed that lecanemab treatment reduced amyloid levels in the patients' plasma and cerebrospinal fluid. Positron emission tomography likewise showed that at 18 months, amyloid levels had dropped below the positivity threshold. As its primary metric for lecanemab efficacy, Clarity AD used CDR-SB, a validated scale used in many Alzheimer's trials. The CDR-SB score is obtained through interviews with patients and their care partners and evaluates cognition across six domains: memory, orientation, personal care, home and hobbies, community affairs and judgment and problem-solving. While these domains have been established as important and relevant for the patients and caregivers, a New England Journal of Medicine article published Tuesday, along with the CTAD presentation, reported that "a definition of clinically meaningful effects in the primary endpoint of the CDR-SB score has not been established." Despite meeting its predefined treatment target, Clarity AD needs to be followed up with longer trials "to determine the efficacy and safety of lecanemab in early Alzheimer's," the authors of the NEJM article recommended.