Galantamine Hydrobromide

*仅供医学专业人士阅读参考我们知道，胆碱酯酶抑制剂（ChEI，如多奈哌齐、卡巴拉汀）是临床上治疗轻到中度阿尔茨海默病（AD）的常见治疗药物。但根据近年来的数据，临床上约有不到一半的遗忘型轻度认知障碍（aMCI）患者因担心疾病进展，也开始服用ChEI。但aMCI患者到底适不适合用ChEI治疗，目前还存在争议。近期，首都医科大学宣武医院贾建平团队发表了一项研究，就深入探讨了aMCI患者服用ChEI是否可以延缓疾病进展，以及分析了ChEI对aMCI患者认知功能的影响。结果发现，在纳入的558名aMCI患者（其中168名患者接受了ChEI治疗）中，与未使用ChEI治疗相比，使用ChEI治疗与aMCI向AD进展的风险增加77%有关。此外，接受ChEI治疗的aMCI患，认知功能衰退速度明显更快，且纵向分析显示，接受ChEI治疗前后，aMCI患的认知功能呈现持续下降趋势（即下降趋势在治疗前已开始，治疗后仍在持续）。更重要的是，研究人员还发现，ChEI治疗与Aβ负担是两个独立的影响aMCI向AD进展的因素，且两者之间不存在显著交互作用。总之，这一结果表明，aMCI患者使用ChEI治疗既不能延缓疾病进展，也不能减缓认知功能下降的速度。提示，对于aMCI患者而言，临床上使用ChEI还需谨慎考虑。研究发表在Alzheimer’s & Dementia上[1]。为了探讨了aMCI患者服用ChEI是否可以延缓疾病进展，以及分析了ChEI对aMCI患者认知功能的影响，研究从阿尔茨海默病神经影像学倡议（ADNI）数据库中纳入了558名aMCI患者，这些患者平均年龄为72.1岁，女性占比42.65%，其中共有168患者接受了ChEI治疗（接受ChEI治疗的定义为，使用多奈哌齐、卡巴拉汀或加兰他敏超过12个月，且至少有两次随访记录）。此外，研究还单独纳入了63位在随访中开始使用ChEI，并连续使用1年以上的aMCI患者数据，用于分析ChEI治疗前后，aMCI患者的认知功能变化情况（认知功能变化用临床痴呆评定量表CDR-SB评分，简易精神状态量表MMSE评分和阿尔茨海默病评估量表-认知子量表13，即ADAS-Cog-13评分评估，其中CDR-SB和ADAS-Cog-13评分越高、MMSE分数越低，表示认知功能越差）。结果显示，在随访期间，共有138名aMCI患者进展为AD，其中接受ChEI治疗的aMCI患者进展为AD的风险明显更高（调整后的HR=1.77，p=0.001）。在认知功能变化方面，线性混合效应模型分析表明，接受ChEI治疗的aMCI患者的认知衰退速度明显快于未接受治疗的aMCI患者（具体表现为，与未接受治疗的患者相比，接受ChEI治疗的aMCI患者CDR-SB年均增加0.35分，ADAS-cog13年均增加0.80分，MMSE年均下降0.38分，p值均<0.001）。而在治疗前后，认知功能的纵向变化趋势上，研究人员发现，aMCI患者在接受ChEI治疗前的5年内，认知功能就已经开始下降。然而，在启动ChEI治疗之后，aMCI患者认知功能并未得到改善，反而持续下降（表现为CDR-SB与ADAS-cog13评分持续上升，MMSE评分持续下降）。而当研究人员进一步按基线Aβ状态进行分层后发现，无论是Aβ阴性还是Aβ阳性的aMCI患者，ChEI治疗后均表现出持续的认知下降。此外，研究并未发现ChEI治疗与Aβ负担之间存在显著交互作用。中介分析也显示，ChEI对aMCI患者疾病进展的影响并非通过Aβ积累途径间接实现，而是独立的。提示，ChEI治疗与Aβ负担是两个独立的影响aMCI向AD进展的因素。总之，该研究证实，aMCI患者使用ChEI治疗既不能延缓疾病进展，也不能减缓认知功能下降的速度。这一发现也提示，临床上应重新审视ChEI在MCI阶段的使用价值。不过本文作者也呼吁，未来希望能通过前瞻性、大样本、长期随机对照试验来进一步科学地评估ChEI在不同认知障碍群体中的真实疗效和获益情况。参考文献：[1]Liu W,Li Y,Qin W,et al.The impact of cholinesterase inhibitors on cognitive trajectories in mild cognitive impairment patients based on amyloid beta status.Alzheimer's Dement.2025;21:e70193.https://doi.org/10.1002/alz.70193本文作者丨张金旭

Launched ZUNVEYL (benzgalantamine) to US market on March 17, 2025 Secured business development licensing revenues of $2.6M for partnership with CMS Pharma Cash and cash equivalents of $45.5 million as of March 31, 2025, compared to $48.6 million as of December 31, 2024. At current cash utilization rates, the Company expects a cash runway of approximately two years. Vancouver, BC — (BUSINESS WIRE) — May 15th, 2025 — Alpha Cognition Inc. (Nasdaq: ACOG) (“Alpha Cognition”, or the “Company”) today announced its financial results for the first quarter ended March 31, 2025. “We closed the quarter on a strong note, launching ZUNVEYL® to the long-term care market,” said Michael McFadden, Chief Executive Officer. “We feel that the company is operating at a high level and are on schedule and within budget on all of our launch plans. Early market feedback on ZUNVEYL utilization reinforces our belief that ZUNVEYL can be a disruptive product for the Alzheimer’s segment. The team is reporting successful patient stories that fuel our passion to tell more health care providers about ZUNVEYL.” Recent Business and Operational Highlights: Commercial Readiness: Alpha Cognition launched ZUNVEYL to long term care market on time and within budget. Early clinician feedback underscores ZUNVEYL’s positive impact on cognitive function, established safety profile, and convenient administration. Medicare reimbursement secured shortly after launch, expanding access for long-term care patients. Robust initial demand reflected in broad ordering activity and early product replenishment by wholesalers. Order momentum is building, with many accounts already submitting reorders. Field team actively engaging the majority of high-priority long-term care targets nationwide. Strengthened Intellectual Property Portfolio: The Company secured a new composition of matter patent in the U.S., covering the tablet formulation of benzgalantamine. This patent extends ZUNVEYL’s U.S. protection through 2044 and global protection through 2041, enhancing Alpha Cognition’s long-term competitive position. The Company received notice from FDA regarding an extension of a method of use patent. The final extension date is expected to be provided by the agency in Q3 2025. First Quarter 2025 Financial Results: Zunveyl net product revenues of $347 thousand for the quarter ended March 31, 2025. Licensing revenue of $2.6M for the quarter ended March 31, 2025. Research and development expenses for the three months ended March 31, 2025 were $408 thousand compared to $917 thousand for the same period in 2024. Selling, general and administrative expenses for the three months ended March 31, 2025 were $5.4 million compared to $3.5 million for the same period in 2024, driven primarily by commercial-readiness activities. Net loss for the for the three months ended March 31, 2025 were $2.0 million compared to $5.0 million for the same period in 2024 Cash and cash equivalents of $45.5 million as of March 31, 2025 compared to $48.6 million as of December 31, 2024. At current cash utilization rates, the Company expects a cash runway of approximately two years. About Alpha Cognition Inc. Alpha Cognition Inc. is a commercial stage, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (“mTBI”), for which there are currently no approved treatment options. ZUNVEYL is a patented drug approved as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ZUNVEYL’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia, and as an intranasal formulation for Cognitive Impairment with mTBI. For further information: Investor Relations IR@alphacognition.com https://www.alphacognition.com/ INDICATION AND USAGE ZUNVEYL is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type in adults. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS ZUNVEYL is contraindicated in patients with known hypersensitivity to benzgalantamine, galantamine, or to any inactive ingredients in ZUNVEYL. Serious skin reactions have occurred. WARNINGS AND PRECAUTIONS Serious Skin Reactions: Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine (the active metabolite of ZUNVEYL tablets). If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed, and alternative therapy should be considered. Anesthesia: See Drug Interactions Section Cardiovascular Conditions: Cholinesterase inhibitors, including ZUNVEYL, have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. Bradycardia and all types of heart block have been reported in patients taking cholinesterase inhibitors, both with and without known underlying cardiac conduction abnormalities. Therefore, all patients should be considered at risk for adverse effects on cardiac conduction. Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope. Gastrointestinal Conditions: Cholinesterase inhibitors, including ZUNVEYL, may increase gastric acid secretion. Patients should be monitored closely for active or occult gastrointestinal bleeding, especially those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Galantamine has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss. Monitor the patient's weight during therapy with ZUNVEYL. Genitourinary Conditions: Although this was not observed in clinical trials with galantamine, cholinesterase inhibitors, including ZUNVEYL, may cause bladder outflow obstruction. Neurological Conditions: Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. Seizure activity may also be a manifestation of Alzheimer's disease. Patients with Alzheimer's disease should be monitored closely for seizures while taking ZUNVEYL. Pulmonary Conditions: Cholinesterase inhibitors, including ZUNVEYL, should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease. Monitor for respiratory adverse reactions. ADVERSE REACTIONS The most common adverse reactions with galantamine tablets (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite. DRUG INTERACTIONS Use with Anticholinergics: Galantamine has the potential to interfere with the activity of anticholinergic medications. Use with Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data may cause fetal harm. Hepatic Impairment: In patients with moderate hepatic impairment, a decrease in clearance of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with severe hepatic impairment is not recommended. Renal Impairment: In patients with a creatinine clearance of 9 to 59 mL/min, an increase in exposure of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with creatinine clearance less than 9 mL/min is not recommended. These are not all of the possible side effects of ZUNVEYL. You can report side effects to the FDA. Visit www.fda.gov/MedWatch or call 1‑800‑FDA‑1088. Please click here for Full Prescribing Information. Forward-looking Statements This news release includes forward-looking statements within the meaning of applicable securities laws. Except for statements of historical fact, any information contained in this news release may be a forward‐looking statement that reflects the Company’s current views about future events and are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. In some cases, you can identify forward‐looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward‐looking statements may include statements regarding the potential benefits of the licensing agreement for the development and commercialization of ZUNVEYL in Asia (excluding Japan), Australia and New Zealand, the Company’s timing and planned activities to launch ZUNVEYL in the U.S. and China, the timing for the Company’s planned corporate update call, the potential timing for the availability of ZUNVEYL in the U.S. and China, the potential future developments of ZUNVEYL in China, the potential market size for ZUNVEYL in China, the Company’s business strategy for the launch of ZUNVEYL in China, the market size and demand for ZUNVEYL in China, the Company’s potential growth opportunities in China, the timing and results of the Company’s milestone payments for China, the Company’s regulatory submissions in China, and the potential regulatory approval and commercialization of the Company’s products in China. Although the Company believes to have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements. These forward-looking statements are subject to certain risks, including risks regarding our ability to raise sufficient capital to implement our plans to commercialize ZUNVEYL, risks regarding the efficacy and tolerability of ZUNVEYL, risks related to ongoing regulatory oversight on the safety of ZUNVEYL, risk related to market adoption of ZUNVEYL, risks related to the Company’s intellectual property in relation to ZUNVEYL, risks related to the commercial manufacturing, distribution, marketing and sale of ZUNVEYL, risks related to product liability and other risks as described in the Company’s filings with Canadian securities regulatory authorities and available at www.sedar.com and the Company’s filings with the United States Securities and Exchange Commission (the “SEC”), including those risk factors under the heading “Risk Factors” in the Company’s Form S-1/A registration statement as filed with the SEC on November 6, 2024 and available at www.sec.gov. These forward‐looking statements speak only as of the date of this news release and the Company undertakes no obligation to revise or update any forward‐looking statements for any reason, even if new information becomes available in the future, except as required by law.