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 Insights - Early use of the drug Donanemab significantly benefits Alzheimer's patients, reducing the risk of disease progression to the next stage by 27% compared to those who start treatment later [1] Group 1: Drug Efficacy - Over 75% of early users of Donanemab achieved amyloid clearance within 76 weeks of treatment [2] - The rate of amyloid plaque re-deposition in patients who completed treatment was approximately 2.4 CL/year over a maximum observation period of 2.5 years [2] - Long-term follow-up showed no new safety signals during the extended phase of the study [2] Group 2: Safety Concerns - Previous treatments targeting amyloid have shown imaging-related abnormalities (ARIA), including edema/exudate (ARIA-E) and bleeding/hemosiderin deposition, which may lead to severe symptoms [2] - Brain swelling and bleeding related to amyloid-clearing drugs primarily occur within the first six months of treatment [2] Group 3: Market Context - Donanemab was officially introduced for clinical treatment in China at the end of March this year, with ongoing validation of its long-term efficacy in the Chinese patient population [2] - Another Alzheimer's drug, Lecanemab, has been in clinical use in China for over a year, showing a 34% slower cognitive decline compared to untreated patients after four years [3] - China has approximately 9.83 million Alzheimer's patients, with an estimated 20% being in the early stages of the disease, potentially benefiting from innovative treatments [3]

Core Viewpoint - The National Health Commission of China has banned the use of "Lymphatic-Venous Anastomosis (LVA)" for the treatment of Alzheimer's disease due to a lack of long-term, statistically significant safety and efficacy data [1][2][15]. Group 1: Background of LVA Surgery - LVA surgery is not a new procedure; it was originally developed in the late 20th century for treating lymphatic diseases like lymphedema [2][12]. - The application of LVA for Alzheimer's treatment began in 2018 by Dr. Xie Qingping, leading to its widespread adoption in various medical institutions [2][12]. - Prior to the ban, over a hundred hospitals had been performing LVA surgeries, with total cases exceeding a thousand [7][12]. Group 2: Financial Aspects and Demand - The cost of LVA surgery ranges from tens of thousands to over 210,000 yuan, with many hospitals charging between 20,000 to 50,000 yuan [12][9]. - The financial burden of long-term care for Alzheimer's patients often makes LVA surgery an attractive option for families, as it can be more cost-effective compared to ongoing care [12][9]. - Hospitals have been motivated to promote LVA surgery due to the potential for significant revenue generation, especially in light of financial struggles faced by many medical institutions [12][13]. Group 3: Regulatory and Clinical Concerns - The rapid promotion of LVA surgery occurred in a regulatory vacuum, with many institutions conducting the procedure without sufficient clinical trial data to support its safety and efficacy [14][15]. - The National Health Commission's ban highlights the need for rigorous clinical trials and ethical guidelines for new treatments, as many hospitals had been charging for a procedure that lacked proper validation [15][16]. - There are currently only 12 registered clinical trials for LVA surgery in Alzheimer's treatment, indicating a significant gap in clinical research [15][16].

Core Viewpoint - The production of the Alzheimer's drug "Jiuyiqi" by Green Valley Pharmaceutical has been halted due to the expiration of its license, prompting concerns among patients about when it will resume production. The drug is required to supplement its Phase III clinical data, which has been deemed insufficient [1][2]. Group 1: Clinical Trial and Regulatory Issues - The initial Phase III clinical trial for "Jiuyiqi" was conducted over a period of only 9 months, which has raised significant concerns regarding its adequacy compared to international standards that typically require two parallel trials [1][2]. - The drug was conditionally approved in November 2019, with the understanding that additional data, including a long-term carcinogenicity study in rats, would be submitted within three months. This data has since been provided, showing no carcinogenic risk [2]. - Due to the COVID-19 pandemic, the originally planned global clinical trials were reduced to a smaller scale conducted domestically, which has led to questions about the rigor of the trial design [3]. Group 2: Market Context and Competitive Landscape - Since the launch of "Jiuyiqi," it has been included in the medical insurance system, significantly reducing the monthly treatment cost from over 1500 RMB to under 300 RMB [4]. - In the past year, new Alzheimer's treatments such as Lecanemab and Donanemab have been approved, but they come with high annual treatment costs of around 200,000 RMB and are not yet covered by insurance [4]. - There is a strong call within the industry for domestic manufacturers to continue investing in innovative Alzheimer's drug development to address the substantial unmet clinical needs, as existing treatments are either expensive or ineffective for late-stage diseases [4].