智通财经APP获悉，诺和诺德(NVO.US)计划在今年年底前公布两项针对轻度阿尔茨海默病患者的后期 研究结果。这些试验使用的是口服司美格鲁肽，这是该公司重磅糖尿病药物Ozempic和减肥药Wegovy的 关键成分。研究结果可能对该公司股票产生重大影响。 在分析了回顾性研究数据后，丹斯克银行分析师认为试验有可能取得积极成果。分析师表示："有迹象 表明 GLP-1 确实具有某种认知保护作用。我们认为这一点值得投资者考虑，尤其是在诺和诺德当前股 价的背景下。" 阿尔茨海默病药物研发极为困难，多年来已有数百项颇具前景的研究以失败告终。尽管近期取得了一些 突破性进展，但目前仍无药物能够预防或逆转该病症。这种病症会导致毁灭性的认知能力下降、记忆丧 失及性格改变。 尽管美国监管机构在过去三年批准了两种治疗阿尔茨海默病的新药，但这些药物只能减缓病情进展约三 分之一。此外，这些药物还可能导致罕见但有时会致命的脑部出血。 Edmond de Rothschild Asset Management投资组合经理Sebastien Malafosse表示："如果结果积极，我预计 股价将大幅上涨。这将是一个巨大的惊喜。" 摩根士丹利分析 ...

Summary of Innovus Bio Conference Call Company Overview - **Company**: Innovus Bio - **Drug**: Buntanetab - **Indication**: Alzheimer's Disease - **Current Phase**: Phase three pivotal study Key Points and Arguments Alzheimer's Drug Development Landscape - Historical context: Several drugs developed around 2000 improved cognition short-term, followed by a 20-year period with no approvals [2][3] - Recent approvals focus on slowing cognitive decline rather than improving cognition [3] - Over 180 ongoing Alzheimer's studies indicate a surge in drug development [3] Buntanetab's Unique Mechanism - Buntanetab is positioned as a disease-modifying drug that improves cognition short-term while protecting nerve cells long-term [4][7] - It is orally available, easy to administer, and has no side effects [8] - Targets four toxic proteins associated with Alzheimer's: plaque, tau, alpha-synuclein, and TDP-43 [11][12] - Acts on mRNA to inhibit the synthesis of these proteins, differentiating it from existing drugs [12] Efficacy in Animal Studies - Demonstrated both symptomatic and disease-modifying efficacy in eight different animal models [23] - Protects nerve cells from dying in traumatic brain injury and glaucoma models [21][22] Human Clinical Trials - Conducted 12 studies in humans, including small studies in healthy volunteers and early Alzheimer patients [23] - Small studies showed significant improvement in cognition compared to placebo, with a 3.5 to 4.5 ADS cog points improvement [25] - A larger study with 350 patients did not meet primary endpoints but showed a significant dose-response curve in early moderate patients [26][27] - Ongoing large study with 760 early Alzheimer patients lasting 18 months, with dual endpoints for symptomatic and disease modification [36] Comparison with Existing Treatments - Buntanetab shows a 3 to 4 point improvement in ADS cog at three months, compared to existing drugs like Aricept and Kisumbla, which show limited efficacy over time [31][34] - The drug works effectively across various demographics, including APOE4 positive and negative patients [27][28] Future Outlook - Anticipated NDA filings: Six-month data by the end of next year and 18-month data by 2027 [36] - The study design includes both symptomatic and disease-modifying endpoints, with a focus on volumetric MRI and biomarkers [37] Intellectual Property - Innovus Bio has 13 patent families extending patent life until 2044, including a novel crystal form developed last year [38] Additional Important Information - The drug's mechanism improves axonal transport, which is crucial for cognitive function [15][20] - Inflammation reduction is achieved indirectly by keeping nerve cells healthy, thus preventing immune system attacks [19][20] - The drug's efficacy is supported by biomarker improvements in neurofilament light and inflammatory factors [30]

Core Viewpoint - The approval process for the first domestically developed Alzheimer's drug, "Jiuyiqi" (Glycyrrhizin Sodium Capsules), has encountered significant setbacks, indicating challenges in the drug's re-registration and the broader difficulties in Alzheimer's drug development in China [1][7]. Approval Challenges - "Jiuyiqi" was conditionally approved in November 2019 for treating mild to moderate Alzheimer's disease, but its re-registration application has not been approved, as indicated by the absence of an approval number in the recent notification from the National Medical Products Administration (NMPA) [1][3]. - The NMPA requires companies to submit a new application for re-registration, and "Jiuyiqi" has faced scrutiny regarding its clinical trial data and the adequacy of its ongoing studies [2][3]. Industry Context - The drug's approval difficulties reflect a global challenge in Alzheimer's drug development, primarily due to the unclear pathogenic mechanisms of the disease and the complexities involved in clinical trials [7][8]. - The pricing of "Jiuyiqi" has made it a more accessible option for patients compared to imported alternatives, which can cost significantly more [7]. Controversies and Legal Issues - "Jiuyiqi" has been surrounded by controversy regarding its efficacy and the reliability of its clinical trials, leading to public debates and legal disputes among key figures in the scientific community [4][5]. - Despite the controversies, the drug was included in the national medical insurance directory, highlighting its perceived value in the market [6]. Future Prospects - The future of "Jiuyiqi" and its potential re-registration remains uncertain, as the company must provide additional data to support its application [7][8]. - The case of "Jiuyiqi" serves as a significant example in the history of original drug development in China, illustrating the complexities and challenges faced by pharmaceutical companies in the Alzheimer's treatment landscape [7][8].

Core Viewpoint - The article discusses the ongoing challenges faced by Green Valley Pharmaceutical regarding its Alzheimer's drug GV-971 (甘露特钠胶囊), which has not received re-registration approval, leading to potential production halts and supply shortages [4][21]. Group 1: Drug Approval and Market Status - GV-971, developed for mild to moderate Alzheimer's disease, was conditionally approved in November 2019, marking the first new Alzheimer's drug approval in 17 years [8]. - The drug has faced significant scrutiny regarding its efficacy and clinical trial data, with notable public disputes among experts [8][9]. - As of May 2023, reports indicated nationwide shortages of GV-971, with prices on e-commerce platforms soaring to 5000 yuan per box, compared to its original price of 296 yuan when included in medical insurance [20]. Group 2: Production and Regulatory Challenges - Green Valley announced in May 2023 that it would halt production of GV-971 due to the expiration of its drug registration certificate, which is typically renewed six months prior to expiration [20][21]. - The failure to secure re-registration approval is believed to be linked to poor clinical trial data or unclear efficacy [21]. - The company has faced criticism for its handling of the drug's international clinical trials, which were suspended in May 2022 [8][9]. Group 3: Patient Impact and Alternatives - Patients have expressed concerns over the potential impact of drug shortages, but experts suggest that the drug's mechanism does not lead to immediate adverse effects upon discontinuation [21]. - Alternatives for patients include symptom-targeting medications and non-pharmacological interventions, although no similar mechanism drugs have been approved [21].

Core Viewpoint - The re-registration application for GV-971 (甘露特钠胶囊) by Green Valley Pharmaceutical has been denied, marking a significant challenge for this Alzheimer's disease drug that has been controversial since its conditional approval in 2019 [1][4]. Company Summary - GV-971, developed by Green Valley, is aimed at improving cognitive function in patients with mild to moderate Alzheimer's disease. It was conditionally approved in November 2019, filling a 17-year gap in new Alzheimer's drug approvals [1][2]. - The drug's approval was based on its unique mechanism targeting the gut-brain axis, using low molecular weight acidic oligosaccharides derived from marine brown algae, differing from the mainstream β-amyloid hypothesis [2]. - Following the denial of the re-registration application, Green Valley's production has been halted, and the drug has faced supply shortages and price increases across various platforms [1][4]. Industry Summary - The denial of GV-971's re-registration reflects the complexities involved in the development and approval of Alzheimer's drugs, highlighting potential issues with clinical trial data and efficacy [4][5]. - The drug's conditional approval required the completion of clinical trials and submission of formal reports, which have not been satisfactorily met, leading to the current situation [2][3]. - There are currently no other drugs with a similar mechanism approved, although alternative symptomatic treatments are available, such as donepezil, which some patients have switched to following GV-971's supply issues [5].

Core Viewpoint - Wanbangde Pharmaceutical Holdings Group Co., Ltd. has launched a national conference for the Phase II/III clinical trial of its new drug Huperzine A controlled-release tablets for Alzheimer's disease, emphasizing the importance of local research and collaboration among experts [1][2]. Group 1: Clinical Trial Launch - The national launch conference for the Phase II/III clinical trial of Huperzine A controlled-release tablets was held in Beijing [1]. - Experts gathered to discuss the significance of the trial and to collaborate on high-quality development of the drug [1]. Group 2: Research and Development Insights - Professor Jia Jianping highlighted the trial's importance and encouraged local researchers to take pride in their work [1]. - Zhao Guanjia, the director of Wanbangde's research institute, discussed the company's focus on Huperzine A and its extensive groundwork in related research [1]. Group 3: Safety and Efficacy - Researcher Gan Yong shared the development history of Huperzine A controlled-release tablets, noting the urgent need for effective and well-tolerated drugs for Alzheimer's patients [2]. - Director Yan Feng provided insights into the safety profile of the drug, indicating that preliminary data supports its good safety and pharmacological characteristics [2]. Group 4: Training and Standardization - The conference included comprehensive training on the research protocol, operational processes, and key execution points to ensure a unified understanding among all researchers [2].

Core Viewpoint - The development of Alzheimer's drugs is facing significant bottlenecks, with Biogen and Eli Lilly maintaining a leading position in the market. However, due to research setbacks, safety risks, and slow adoption, the market size forecast for 2030 has been drastically reduced to $6 billion from a previous expectation of $13 billion [3][4]. Group 1: Market Forecast and Sales Predictions - The combined sales of Biogen's Leqembi and Eli Lilly's Kisunla are projected to reach $5.91 billion by 2025, with potential growth to $40 billion by 2030, which is 24% lower than the market's general expectation of $50 billion due to slow drug adoption [4]. - By 2030, the total sales of Alzheimer's drugs are expected to reach $6 billion, with nearly $1 billion coming from new mechanism drugs [5]. Group 2: Impact of Research Failures - A series of late-stage clinical trial failures have led to a 54% reduction in sales forecasts for Alzheimer's drugs since June 2024, with risk-adjusted sales expectations shrinking by over $7 billion for 2025-2030, including a $3 billion reduction for 2030 alone [8][11]. - The decline in sales expectations is attributed to the exit of several late-stage candidates from the market due to research failures or lowered priorities [8]. Group 3: Competitive Landscape - The long-term administration of Leqembi shows limited cognitive improvement, particularly in patients with low or no tau pathology, which affects about 40% of the trial population. This has led to skepticism among physicians and patients regarding the drug's efficacy [11]. - New candidates, such as Novo Nordisk's semaglutide and Roche's trontinemab, are expected to increase competitive pressure, potentially limiting the market share of first-generation amyloid-beta antibodies [11][15]. Group 4: Company-Specific Insights - Biogen's Leqembi faces increasing risks due to limited application, with sales forecasts for 2030 being 20% lower than market expectations, driven by safety concerns and access barriers [13]. - Eli Lilly is expected to surpass Biogen in sales by 2029, driven by the approval of Kisunla and subsequent antibody drugs, indicating a shift in market leadership [15].

Core Viewpoint - Fosun Pharma's stock has increased by over 4%, reaching HKD 20.15 with a trading volume of HKD 201 million, following the announcement of a licensing agreement with NewCo for the development of AR1001 for Alzheimer's disease and other neurological disorders [1] Group 1: Licensing Agreement - Fosun Pharma's subsidiary has signed a licensing agreement with NewCo, granting rights for the development, registration, production, and commercialization of AR1001 in mainland China and Hong Kong-Macau for Alzheimer's disease and other neurological conditions [1] - Fosun Pharma will pay up to RMB 150 million to NewCo for this licensing agreement [1] Group 2: Clinical Trials - The drug AR1001 was licensed from AriBioCO.,Ltd. by NewCo, which will continue its development [1] - NewCo obtained exclusive rights for AR1001 in Greater China in early 2024 and is collaborating with AriBio to conduct global Phase III clinical trials targeting early Alzheimer's disease patients [1] - The global trial has completed recruitment in 13 countries and regions, including North America, Europe, the UK, China, and South Korea, with approximately 1,500 patients recruited worldwide [1]

每经记者｜许立波 每经编辑｜张海妮 6月23日，有媒体报道，先声药业（HK02096，股价11.220港元，市值277.66亿港元）对阿尔茨海默病 （AD）药物的研发已经停止。2021年6月29日，先声药业与Vivoryon Therapeutics公司宣布建立战略区 域许可合作伙伴关系，以在大中华区进行两款阿尔茨海默病药物的开发及商业化。 有消息人士向《每日经济新闻》记者透露，先声药业阿尔茨海默病相关的研发项目"没有正式停止"。记 者查询发现，在先声药业网站与年报中均已搜索不到上述研发管线。 值得注意的是，早在去年3月Vivoryon披露的Varoglutamstat治疗早期阿尔茨海默病IIb期临床试验 （VIVIAD研究）中，该药物就被证明对AD患者无显著疗效。 阿尔茨海默病药物已从先声药业的重点管线中淡出 资料显示，先声药业是一家创新与研发驱动的制药公司，聚焦神经科学、抗肿瘤、自身免疫及抗感染领 域。阿尔茨海默病是一种中枢神经系统的退行性病变，先声药业进入阿尔茨海默病领域可以追溯到2021 年，是最早引入AD创新药管线的国内企业之一。 彼时，先声药业与德国专注于开发小分子创新药的生物技术公司Vivory ...

Core Viewpoint - The news highlights the supply issues surrounding GV-971 (甘露特钠胶囊), a drug for Alzheimer's disease, which has led to a significant price increase and potential production halt due to regulatory challenges and cash flow problems faced by the manufacturer,绿谷制药 [1][3][5]. Group 1: Supply and Demand - GV-971 has been experiencing a supply shortage since six months ago, with recent reports indicating complete stockouts, causing prices to surge from 296 yuan to between 830 yuan and 1,033 yuan per box [1]. - Over 9,300 patients have requested the drug, and more than 1,200 doctors have urged the company to ensure continuous supply [1]. - The company is in communication with relevant authorities to expedite the review process for the drug's certification renewal [1][2]. Group 2: Regulatory and Clinical Background - GV-971 was conditionally approved in November 2019, becoming the first drug targeting the "gut-brain axis" mechanism for Alzheimer's treatment [3]. - The drug's approval was contingent upon the submission of long-term carcinogenicity data, which was completed and submitted in December 2019, showing no carcinogenic risk [3]. - The drug has been under review since October 2024, but its approval status remains pending, possibly due to ongoing debates regarding its efficacy [4]. Group 3: Financial Performance and Market Impact - Since its launch, GV-971 has reportedly benefited over 500,000 patients, with sales reaching 2.13 million boxes in 2024 alone [5]. - The drug's sales have grown at a compound annual growth rate of 343.2% since its approval, with hospital sales reaching 170 million yuan and retail sales at 156 million yuan in 2022 [5]. - The company has faced severe cash flow issues, leading to temporary layoffs and reduced salaries for employees [2]. Group 4: Alternative Treatments and Market Landscape - Despite the supply issues with GV-971, other established treatments for Alzheimer's disease, such as cholinesterase inhibitors and NMDA receptor antagonists, remain available [6]. - Newer drugs like Eli Lilly's donanemab and Eisai's lecanemab have also entered the market, providing additional options for patients [7]. - The Alzheimer's drug development landscape is characterized by high investment and risk, with over $100 billion invested globally, yet only one drug successfully launched from over 200 clinical trials [8][9].