Buntanetap

▲点击图片，了解详情 作者：黄仲平 随着社会的前进和生活质量的提升，人类的预期寿命在不断增长，老龄化的步伐也在加快，随之而来的是中枢神经系统（CNS）疾病的发病率也在逐步上升，如帕金森病和阿尔兹海默症等老年性疾病对人类的健康和生活质量构成了严重威胁。同时，生活节奏的加快和竞争的加剧带来了更大的精神压力，这导致了失眠和抑郁症等精神障碍的发病率急剧增加。 不断上升的患病数量为全球中枢神经类药物市场不断扩容，正在催化越来越多的CNS新药诞生。 遗忘得到减缓 对中国的阿尔茨海默症患者来说，2024年是个幸运年：年初，卫材的仑卡奈单抗（Lecanemab）登场；年末，礼来的多奈单抗（Donanemab）获批。不过这也意味着，仑卡奈单抗和多奈单抗将在中国市场产生正面碰撞，谁能更胜一筹？ 仑卡奈单抗针对早期阿尔兹海默症的Ⅲ期试验结果显示：接受治疗18个月后，仑卡奈单抗组和安慰剂组的临床痴呆评分总和（CDR-SB）评分分别为1.21和1.66。相较安慰剂组，仑卡奈单抗组CDR-SB评分低0.45，评分增速降低了27%。基于观察到的数据和外推至30个月的CDR-SB进行的斜率分析，接受仑卡奈单抗治疗25.5个月相当于安慰剂治疗18个月时的水平，这表明仑卡奈单抗可以延缓疾病进展达7.5个月。 多奈单抗的III期临床研究TRAILBLAZER-ALZ 2结果显示：与安慰剂组相比，接受多奈单抗治疗组患者的综合阿尔茨海默病评定量表（iADRS）评分下降速度减缓了35%，临床痴呆评定量表总和评分（CDR-SB）较安慰剂组下降速度减缓了36%，并且阿尔茨海默病合作研究日常生活活动量表（ADCS iADL）评分显示疾病进展速度延缓了40%。 单纯从数据上看，两者并没有特别显著的差异。 全球市场中，还有一款阿杜卡尼单抗（Aducanumab）于2021年6月获美国FDA批准上市。但阿杜卡尼单抗商业化表现远低于市场预期，2021年和2022年销售额仅有300万美元和480万美元。雪上加霜的是，多奈单抗在头对头试验中击败了阿杜卡尼单抗，几乎截断了其商业化前景。 阿杜卡尼单抗、仑卡奈单抗和多奈单抗临床数据对比， 来源：太平洋证券研报 这三款近年诞生的阿尔茨海默症新药均为Aβ单克隆抗体，使得以β-淀粉样蛋白斑块为靶点的治疗策略成为主流。 但这并不意味着这一路线就是绝对正确。 阿尔茨海默症的发病机制复杂，至今仍未完全破译具体机制。目前致病机制主要存在三大主流假说：Aβ类淀粉样蛋白级联假说、Tau蛋白异常磷酸化假说和胆碱能假说。三大假说均出现了多条针对性的技术路线。 据统计，全球阿尔兹海默病在研新药超600款，多路线正在齐头并进。 Remternetug是礼来的一款给药方式灵活的靶向N3pG淀粉样蛋白亚型的抗体药物；ALZ-801是Alzheon研发的一款针对淀粉样蛋白聚集和神经毒性的口服小分子抑制剂；Galectin-3是TrueBinding研发的一种可溶性的β-半乳糖苷结合蛋白；Semorinemab是一种人源化的抗tau IgG4单克隆抗体，由基因泰克开发；Atuzaginstat是一款牙龈菌蛋白酶（gingipain）抑制剂，可以降低牙龈卟啉单胞菌毒性，降低细菌负荷，从而改善阿尔茨海默症进展；ATH-1017是一种小分子药物，旨在增强肝细胞生长因子在其受体MET上的活性，由Athira Pharma开发等等等等。 国内方面，2019年11月上海绿谷研发的甘露特纳获批上市，通化金马的1.1类新药AChE抑制剂琥珀八氢氨吖啶已提交NDA。 除此之外，国内自研生物创新药和化学创新药多数尚处于早期临床阶段，研发靶点也呈现多样化态势，并且出现了中药产品。恒瑞医药的国产Aβ单抗SHR-1707处于Ib期临床；先声药业从Vivoryon Therapeutics引进的一种靶向神经毒性淀粉样蛋白N3pE(pGlu-Aβ)的口服小分子谷氨酰肽环转移酶（QPCT）抑制剂处于临床Ⅱb期；康弘药业的6.1类中药创新药KH110（五加益智颗粒）处于临床Ⅱ期；悦康药业的中药1.1类新药复方银杏叶片进入NDA阶段...... 尽管在研发方面，各种路线都在十分努力地证明自己，但从临床试验数据中我们也看到，这些都不是治疗阿尔兹海默症真正有效的药物。道路总是曲折的，随着越来越多的新药上市，曙光似乎就在眼前。 颤抖得到减轻 帕金森病是继阿尔茨海默症后第二常见的神经系统退行性疾病，主要以黑质多巴胺能神经元进行性退变和路易小体形成的病理变化，以及纹状体区多巴胺递质降低、多巴胺与乙酰胆碱递质失平衡的生化改变为显著特征。 临床主要表现为震颤、肌强直、动作迟缓、姿势平衡障碍的运动症状和睡眠障碍、嗅觉障碍、自主神经功能障碍、认知和精神障碍等非运动症状。流行病学调查研究显示欧美国家60岁以上帕金森病患病率达到1%，80岁以上超过4%，我国65岁以上人群患病率为1.7%。 迄今为止，帕金森病的治疗仅能改善症状，无法阻止病情发展。 由于目前帕金森病发病机制并不明确，因此对帕金森病研发也存在多种技术路线之争，主要包括对症治疗（ST）路线和疾病修饰疗法（DMT）路线。 全球范围内，帕金森病在研管线阶段及靶点分类， 来源：太平洋证券研报 从靶点分类看，对症治疗（ST）仍以多巴胺能靶点为主，目前有多个在研处于III期阶段，其中艾伯维开发的ABBV-951（foslevodopa/foscarbidopa）和Cerevel开发的Tavapadon关注度较高。 ABBV-951是一款左旋多巴和卡比多巴前体药物，可显著改善晚期帕金森病患者的运动并发症，已于2024年10月获美国FDA批准上市，是首款基于左旋多巴的24小时皮下连续输注疗法；Tavapadon为一款高选择性D1/D5受体部分激动剂，有潜力成为早期帕金森病单药治疗和晚期帕金森病辅助治疗药物。 随着对帕金森病发病机制的深入研究，疾病修饰疗法（DMT）逐渐成为近年来新药研发的热点。其中也存在多种不同方向技术路线，包括的对热门靶点α-突触核蛋白（α-syn）的研究，以及细胞疗法、肠道菌群疗法、GLP-1受体激动剂等。 Buntanetap是Annovis Bio开发的一种可阻断mRNA翻译表达神经毒性蛋白的小分子抑制剂；IKT-148009是一种小分子c-Abl激酶抑制剂，可降低c-Abl激酶的活性；Lu AF82422是一种靶向α-syn C末端的人免疫球蛋白G1（IgG1）单克隆抗体；BIIB122是Denali开发的一款小分子LRRK2激酶抑制剂...... 国内方面，目前已有多款创新制剂上市，以及超21款帕金森病在研新药物。其中以跃赛生物的干细胞技术和恒瑞医药的双基因药物最为受关注。 跃赛生物自主研发针对帕金森病的iPSC来源细胞药物产品UX-DA001注射液（人中脑多巴胺能神经前体细胞注射液）获得CDE的临床试验默示许可，成功进入临床试验阶段，这一突破标志着国内在神经退行性疾病治疗领域的一项重要进展。 RGL-193是恒瑞医药自主研发的一款候选双基因AAV治疗药物，采用立体定向技术注入患者脑内，提高左旋多巴的转化效率，目前已完成首例患者给药。 从市场规模看，目前国内帕金森病仅30余亿元，对标发达国家，渗透率有非常大的增长空间。随着人口老龄化程度持续加深，帕金森病患者人数将快速增加，具有明确疗效的新药不断获批，市场规模或将迎来大规模跃升。 新机制药物接二连三诞生 在治疗手段上，与肿瘤、自身免疫性疾病等相比，CNS领域药物研发进度缓慢。但如上文所述，阿尔茨海默病、帕金森病等领域近年来逐渐出现新机制药物获批，研发困境逐步反转，精神分裂症、抑郁症、偏头痛、失眠等领域都迎来或正在迎来诸多突破性进展。 精神分裂症方面，新机制药物KarXT于2024年9月成功获得美国FDA批准，标志着精神分裂症治疗正式进入“后多巴胺”时代。KarXT是继20世纪50年代初第一代抗精神病药氯丙嗪诞生后，70年来首款采用全新作用机制的抗精神病药物。 KarXT最初由Karuna研发，制药巨头BMS看到了这款药物的潜力，于2023年底以140亿美元价格收购Karuna，再鼎医药拥有KarXT的大中华区权益，并正在参与其多个全球临床研究。 抑郁症方面，近年来同样有所突破，临床上有探索新机制和在传统分子上进行再开发的策略。这其中，来自国内制药企业绿叶制药的托鲁地文拉法辛的获批，创造了国产创新药在抑郁症治疗领域取得的里程碑式的“零”的突破。 新机制的探索路径上，针对单胺通路，COMPASS Pathways开发了针对受体的激动剂COMP360；NMDA拮抗剂带代表药物有安非他酮和右美沙芬的复方制剂Auvelity等。 失眠治疗药物方面，新靶点药物上市速度正在加快，成功开发的有食欲素受体拮抗剂和GABAA正向调节剂。食欲素受体拮抗剂代表药物有默沙东的苏沃雷生，Idorsia的Daridorexant；GABAA正向调节剂代表药物有京新药业的地达西尼，于2023年国内获批上市，服用后平均睡眠时间均可延长，不改变睡眠结构，且未发现依赖性、反跳性失眠、戒断症状和药物滥用证据。 结语 由于中枢神经系统不具有再生能力，加之对神经元运作的机制了解并不全面，这也造成了中枢系统疾病新药研发的难度。但自2022年起，CNS领域新机制研发药物日臻成熟，引起了MNC的强烈关注，开始逐步加码CNS领域的收购和BD，除上文提到的BMS收购Karuna外，辉瑞、艾伯维、默沙东等均现大额并购案，眼见着CNS领域的一场争夺战即将打响。国内布局了CNS研发的药企，如翰森制药、绿叶制药或许有望乘风而上。后续发展如何，贝壳社还将持续关注。 参考资料： 1、各大上市公司官网、公告、年报等 2、太平洋证券、招商证券、智银资本等研报 3、《CNS的冰与火之歌》，氨基观察，2024-12-25 4、《每4周注射一次！礼来阿尔茨海默病新药在国内获批》，人民日报，2024-12-18 5、《全国首款！全球第二款!保税区域生物医药产业又传喜报》，上观，2024-12-25 关于贝壳社 贝壳社是国内领先的医健创新创业服务平台，为医健创业者提供全路径创业服务。通过产业空间运营、创业教育、投资孵化、数字化赋能、企业价值增长等服务体系，给医健创业企业提供产业空间、人才战略培养、投融资、产业生态资源、数字化转型等服务。同时，贝壳社布局澳洲，帮助国内生物医药企业加速走向海外；成立“泰格-泰珑-贝壳社企业经营服务中心”为企业成长提供全生命周期的增值服务，提高企业运营效率，加快企业成长发展。我们深度链接政府、科研院所、临床机构、投资机构、第三方服务商、CXO等行业资源，致力于赋能医疗健康创业公司成长，推动创新技术造福人类生命健康。 往 期 推 荐 1 越来越多Biotech发起“独立宣言” 2 多抗：下一个大药发展趋势 _ 3 围猎60亿美元大药 _ *声明：本文仅为作者观点，不构成任何投资建议，且非治疗方案推荐。 投稿请添加小助手：bioclub666

According to DelveInsight's analysis, the market for Down syndrome is anticipated to increase during the forecast period (2024–2034), owing to the launch of emerging therapies such as AEF0217, ACI-24.060, LEUCETTINIB-21, BUNTANETAP, and others and healthcare spending globally. LAS VEGAS, Nov. 26, 2024 /PRNewswire/ -- DelveInsight's Down's Syndrome Market Insights report includes a comprehensive understanding of current treatment practices, Down's syndrome emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Down's Syndrome Market Report According to DelveInsight's analysis, the market size for Down's syndrome was found to be USD 241 million in the US in 2023. In 2023, the United States accounted for nearly 220K prevalent cases of Down's syndrome. The types of Down's syndrome include Trisomy 21, Robertsonian translocation, and Mosaicism. In 2023, among all types, Trisomy 21 accounted for the highest number of prevalent cases in the 7MM. Leading Down's syndrome companies such as AELIS FARMA, AC IMMUNE, PERHA PHARMACEUTICALS, ANNOVIS BIO, APHIOS THERAPEUTICS, and others are developing novel Down's syndrome drugs that can be available in the Down's syndrome market in the coming years. The promising Down's syndrome therapies in the pipeline include AEF0217, ACI-24.060, LEUCETTINIB-21, BUNTANETAP, APH-1104, and others. Discover which therapies are expected to grab the major Down's syndrome market share @ Down's Syndrome Market Report Down's Syndrome Overview Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of an extra copy of chromosome 21. This chromosomal anomaly disrupts normal development, resulting in a range of physical and cognitive differences. The condition is primarily caused by random genetic mutations during the formation of reproductive cells or early embryonic development, though advanced maternal age increases the likelihood of having a child with Down's syndrome. People with Down's syndrome typically exhibit distinct facial features, such as a flattened face, almond-shaped eyes that slant upward, and a small nose. Other common symptoms include developmental delays, intellectual disabilities, and a variety of health issues like heart defects, respiratory and hearing problems, and a higher susceptibility to infections. Despite these challenges, many individuals with Down's syndrome lead fulfilling lives with appropriate support. Diagnosis of Down's syndrome can occur prenatally through screening and diagnostic tests, such as blood tests and ultrasounds in the first and second trimesters, or through more definitive tests like chorionic villus sampling (CVS) and amniocentesis. Postnatal diagnosis is typically confirmed by a physical examination and a karyotype analysis to identify the extra chromosome. Early diagnosis and intervention can help address developmental needs and improve the quality of life for individuals with Down's syndrome. Down's Syndrome Epidemiology Segmentation The Down's syndrome epidemiology section provides insights into the historical and current Down's syndrome patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The Down's syndrome market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of Down's Syndrome Gender-specific Diagnosed Prevalent Cases of Down's Syndrome Type-specific Diagnosed Prevalent Cases of Down's Syndrome Age-specific Diagnosed Prevalent Cases of Down's Syndrome Diagnosed Cases of Down's Syndrome by Clinical Manifestations Down's Syndrome Treatment Market There is no single treatment for Down's syndrome; instead, care plans are customized to address each person's unique physical and intellectual needs, emphasizing their strengths and accommodating their limitations. For some individuals, immediate surgery may be needed after birth to correct heart defects or long-term dietary modifications may be required for digestive concerns. Common interventions include assistive devices such as hearing aids, mobility aids, and adaptive technology to support learning and daily tasks. People with Down's syndrome often face an earlier and more pronounced cognitive decline than the general population. Treatments for Down syndrome-associated dementia (DSAD) may include medications like rivastigmine, galantamine, memantine, and donepezil, which inhibit acetylcholine breakdown, providing notable benefits. Seizure management for those with Down syndrome may involve anticonvulsants like carbamazepine and phenytoin, although these can exacerbate other Down syndrome-related issues. Respiratory problems are also common due to immune deficiencies and respiratory tract abnormalities, often requiring antibiotics or inhaled bronchodilators for effective management. Along with pharmacological treatments, non-pharmacological therapies such as physical, speech, occupational, and behavioral therapies play a vital role in the early development of children with Down syndrome, promoting independence and productivity. Physical therapy aims to improve motor skills, build muscle strength, and enhance posture and balance, laying the groundwork for key abilities. Speech-language therapy focuses on boosting communication skills and addressing physical challenges like low muscle tone to avoid long-term complications. Occupational therapy adapts daily tasks to suit the individual's abilities, teaching crucial skills such as eating, dressing, writing, and using a computer. Emotional and behavioral therapies tackle challenges like frustration from communication barriers, compulsive behaviors, and ADHD by identifying triggers and creating strategies to foster positive behaviors and reduce undesirable ones. To know more about Down's syndrome treatment guidelines, visit @ Down's Syndrome Management Down's Syndrome Pipeline Therapies and Key Companies AEF0217: AELIS FARMA ACI-24.060: AC IMMUNE LEUCETTINIB-21: PERHA PHARMACEUTICALS BUNTANETAP: ANNOVIS BIO APH-1104: APHIOS THERAPEUTICS Discover more about Down's syndrome drugs in development @ Down's Syndrome Clinical Trials Down's Syndrome Market Dynamics The Down's syndrome market dynamics are expected to change in the coming years. The prevalence of Down syndrome has increased with the rise in lifespan over the past three decades. This, along with the combination of several neurological features in Down syndrome patients—such as language impairment, cognition, learning, and memory—has sparked intense neurodevelopmental research. Studies in this area hold promise for improving clinical care and quality of life for individuals with Down syndrome and their families, as well as for assessing ways to enhance communication between parents and children. A thorough understanding of the factors affecting pharmacotherapy in Down syndrome could significantly contribute to better clinical outcomes for these individuals. Furthermore, potential therapies are being investigated for the treatment of Down's syndrome, and it is safe to predict that the treatment space will significantly impact the Down's syndrome market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the Down's syndrome market in the 7MM. However, several factors may impede the growth of the Down's syndrome market. Down syndrome presents unique challenges in clinical treatment, as there is currently no medical cure or approved products available in the market, complicating the treatment process. This complexity is compounded by the lack of appropriate, validated scales to measure progress or side effects in participants with learning disabilities, making it difficult to gauge treatment impact effectively. Furthermore, recruiting participants and their families is challenging, adding to the difficulties in conducting research. Down syndrome is also associated with numerous health problems and high healthcare costs, and individuals may require more intensive monitoring for adverse effects, adherence, and treatment efficacy when managing medications. Conducting clinical studies on the efficacy of psychotropic medications in individuals with Down syndrome is particularly challenging due to the unique language and communication characteristics of this population. Moreover, Down's syndrome treatment poses a significant economic burden and disrupts patients' overall well-being and QOL. Furthermore, Down's syndrome market growth may be offset by failures and discontinuation of emerging therapies, unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact Down's syndrome market growth. Scope of the Down's Syndrome Market Report Therapeutic Assessment: Down's Syndrome current marketed and emerging therapies Down's Syndrome Market Dynamics: Key Market Forecast Assumptions of Emerging Down's Syndrome Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Down's Syndrome Market Access and Reimbursement Download the report to understand which factors are driving Down's syndrome market trends @ Down's Syndrome Market Trends Table of Contents Related Reports Down's Syndrome Epidemiology Forecast Down's Syndrome Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the Down's syndrome epidemiology trends. Down's Syndrome Pipeline Down's Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Down's syndrome companies, including Alzheon, Inc, Connecta Therapeutics, among others. Alport Syndrome Market Alport Syndrome 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 Alport syndrome companies, including Eloxx Pharmaceuticals, Chinook Therapeutics (A Novartis company), Bayer, Calliditas Therapeutics, Evotec , among others. Alport Syndrome Pipeline Alport Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Alport syndrome companies, including Eloxx Pharmaceuticals, Inc., Chinook Therapeutic/Novartis, River 3 Renal Corp., Travere Therapeutics, Inc., Reata Pharmaceuticals, Inc., 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 . 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