Dimethyltryptamine

在阿尔茨海默病(AD,俗称老年痴呆)诊疗领域,长达数十年的研究始终围绕“如何阻止疾病进展”这一核心命题。 以仑卡奈单抗为代表的抗β淀粉样蛋白(Aβ)单克隆抗体的获批,首次实现了该领域有药物能够靶向疾病病理机制治疗并减缓患者的认知与功能衰退的突破,标志着AD治疗正式迈入疾病修饰治疗(DMT)时代。 然而,围绕抗Aβ药物的疗效、风险与成本争议从未停歇,成为领域内亟待厘清的关键议题。 《柳叶刀》AD专辑(The Lancet Series on Alzheimer's disease)第三篇论文中[1],将这一争议置于现代个体化医疗的宏观框架下深入剖析,并创新性地通过“抗Aβ药物与其他疾病成熟生物制剂进行多维度对比”的思路,试图为AD领域搭建客观的价值判断体系。 那么,这场持续已久的“价值之争”,究竟该如何破解? 1 抗Aβ药物的“价值之争” 抗Aβ药物的争议,并非单纯的“疗效好坏”之争,而是源于不同立场下对“治疗价值”的定义与期待存在差异,换句话说,抗Aβ药物究竟值不值?又对谁更有价值? 从疾病视角来看 ,自1906年阿尔茨海默症首次被描述以来,领域内始终在探索更有效的治疗路径。1993年,首个对症治疗药物他克林获批上市后却因肝毒性退市,此后多奈哌齐、美金刚等药物虽能改善认知症状,却始终无法干预疾病进程,这让学界开始思考: 传统治疗路径是否需要突破? 2021年FDA加速批准阿杜卡单抗后遭遇的挫折,更凸显了DMT的探索难度。在此背景下,仑卡奈单抗作为首个能通过清除大脑Aβ、从病理根源干预疾病进程的药物,其问世具有划时代的意义,是AD研究从“基础理论”走向“临床转化”的关键一步,这无疑为领域带来了新的希望。 从临床视角来看 ,对于临床医生而言,核心顾虑在于: 这款全新机制的药物,其获益风险比该如何科学评估?由于DMT在AD领域尚属新事物,临床使用经验不足,传统疗效评价体系是否适用? 仑卡奈单抗关键性Ⅲ期Clarity AD研究[2]显示,治疗18个月可延缓早期患者认知功能下降约27%,CDR-SB评分绝对差值为0.45分。这种统计学获益能否转化为实际的临床获益? 在安全性方面,临床上对淀粉样蛋白相关影像学异常(ARIA)的风险管理尚不成熟,与抗血栓药物联用的相互作用风险该如何规避? 这些问题需要更多的证据来予以回应。 对于照护者而言 ,药物的出现无疑带来了新的期待,若能延缓患者认知衰退,哪怕只是多几个月的清晰交流,对整个家庭都是极大的慰藉。但同时也会产生顾虑:高昂的治疗费用是否在可承受范围内?这种期待与顾虑的平衡,尚需政策支持与医疗体系协同来逐步解决。 因此,抗Aβ药物争议的本质,在于AD领域此前缺乏同类DMT药物作为参照,且疾病本身病程漫长、进展缓慢,导致其长期临床价值和卫生经济学意义尚不明确。 但值得关注的是,肿瘤等其他领域生物制剂已经积累了成熟的临床应用经验,这些“外部参照”或可为抗Aβ药物的价值定位提供关键借鉴,逐步解答当前的疑问与顾虑。 2 通过“外部参照”破解抗Aβ药物争议 在《柳叶刀》论文中[1],选取了四类具有代表性的疾病及对应生物制剂作为“外部参照”,包括以乳腺癌(曲妥珠单抗)、肺癌(帕博利珠单抗)为代表的高发癌症、以多发性硬化症(奥瑞珠单抗)为代表的低发神经系统疾病、以类风湿关节炎(托珠单抗)为代表的低发非神经系统疾病,并根据“疗效-风险-成本-人群”的评估体系进行多维度对比。 从疗效来看 ,抗Aβ药物对核心治疗终点的改善效果与对照疾病生物制剂处于同一水平,均属于“温和但有临床意义”的干预。 对于早期AD患者而言,CDR-SB出现0.45分的评分差异可能意味着“独立性”的变化,如患者能否独立驾车;而将获益时间转化或许更直观:治疗18个月可延缓5～6个月疾病进展,这对保留患者生活自理能力、减轻家庭照护负担具有重要意义。 更关键的是,随着Clarity AD研究四年随访结果出炉[3],以绝对有力的获益进一步证实了DMT的长期获益潜力,打破仑卡奈单抗“获益有限”的质疑。以ADNI作为对照组,仑卡奈单抗治疗18个月、36个月、48个月后的CDR-SB评分获益分别为0.52、1.01、1.75分,获益逐步扩大。前36个月CDR-SB评分获益约为0.5分/18个月,而在36～48个月期间,获益迅速拉开达到了0.74分/12个月。 更令人振奋的是,从绝对数据看, 仑卡奈单抗治疗4年后仍有81.4%的患者维持在轻度AD或MCI状态! 可见,仑卡奈单抗具有重要的临床价值,并在AD治疗中展现出了长期获益的潜力。 从风险来看 ,这几类药物整体安全性可控,然而依旧存在严重不良反应风险,比如肺癌免疫治疗可能引发严重免疫毒性;多发性硬化症治疗可能导致患者出现高死亡率的多灶性白质脑病;类风湿关节炎治疗则可能引起有严重感染与肠穿孔。 由此可见,抗Aβ的ARIA副作用并非不可接受,核心差异在于其他疾病生物制剂的风险“可预测、可预防”,而抗Aβ药物对安全性管理经验仍在积累中,需要进一步完善其风险管控体系。 今年AAIC大会上披露的真实世界数据[4]也印证了仑卡奈单抗具有显著的安全性优势,在真实世界中的ARIA发生率远低于临床研究中的发生率,并且无论AD患者的ApoE基因如何,均能通过接受仑卡奈单抗治疗取得一致的认知衰退延缓、维持病情恶化程度等治疗获益。与此同时,该研究也有证据表明,抗血栓药物并不会增加AD患者使用仑卡奈单抗引起ARIA不可控风险。 从成本来看 ,抗Aβ药物年治疗费用并非最贵,甚至均低于对照疾病生物制剂。并且,药物成本高昂制约其应用与普及这一问题并非抗Aβ药物独有问题,在其他疾病中也曾出现,乳腺癌曲妥珠单抗、类风湿关节炎托珠单抗上市初期均面临类似挑战,最终通过“医保谈判降价+技术迭代降本”实现了可及性提升。这意味着,抗Aβ药物的成本问题可通过成熟路径逐步解决。 值得注意的是,与肿瘤、多发性硬化症、类风湿关节炎等疾病不同,AD的成本中还有很大一部分源自于非医疗支出(如家庭照护、长期护理机构费用),且该成本随疾病严重程度急剧上升,据统计,轻度与重度阶段的年成本差异约为2.5万欧元。 抗Aβ药物对AD疾病进展的延缓可一定程度上降低这一部分非医疗支出,尽管这种成本节约可能是“推迟高成本阶段”而非“完全消除”,但对减轻家庭与社会负担的长期意义仍不可忽视。 从适用人群来看 ,目前抗Aβ药物的适用人群覆盖率较低,但是这里不可忽视的一个背景是抗Aβ药物在AD领域尚属新药物,因此,这个适用人群覆盖率仅为初期阶段数据,并非永久局限。这一现象并非AD领域独有,其他疾病生物制剂初期都仅适用于高度筛选人群,随临床经验积累、循证证据完善,才逐步实现“从窄人群到宽人群”的推广过程。 因此,如果其他疾病的生物制剂能被接受,那么抗Aβ药物也应如此。 3 从争议走向共识 通过与成熟生物制剂对比可见,争议的本质是“新兴疗法适应临床的阵痛”,而非“价值否定”。我们需要正视争议,从争议走向共识,共同推动抗Aβ药物的落地。 对于AD领域而言,抗Aβ药物的意义早已超越一款药物本身,而是推动了整个领域的变革,具有里程碑意义,所以其应像别的生物制剂一样被赋予成长的时间与空间。 在检测技术上,以血浆p-tau217和Aβ42/Aβ40比值为代表的血液检测,解决了传统AD诊断 “侵入性强、成本高”的痛点,并且其检测AD病理的准确率超90%。若未来可大幅推广血检,将显著降低诊疗成本,提升成本效益。 在疾病干预上,DMT具有“越早用药,效果越好”的显著特征,因此,对于早期AD患者而言,尽早接受抗Aβ药物治疗,不仅能更有效地延缓认知衰退,还能最大限度保留生活自理能力,减轻家庭照护负担。一项针对仑卡奈单抗在中国患者群体中应用体验的全国性调查显示[5],在接受了仑卡奈单抗治疗的患者家庭中,94.5%的照护者表示照护负担没有加重,其中,68.7%的照护者认为“照护负担没有变化”,25.8%的照护者明确感受到照料负担减轻。特别是对于子女照护者而言,这种负担缓解效果更为显著。 未来,AD应从“被动治疗”转向“主动预防”,建立“早筛-早诊-早治”路径,从源头上降低发病率和重症AD患者基数,这一改变对照护者与社会负担的减轻不容忽视。 争议不是终点,而是推动AD治疗进步的起点…… 参考文献: 1.Frisoni G B, et al. Alzheimer’s disease outlook: controversies and future directions. The Lancet. 2025, 406: 1424-1442. 2.van Dyck CH, et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023, 388(1): 9-21. 3.Christopher H van Dyck . The Lecanemab Clarity AD Open-Label Extension in Early Alzheimer’s Disease: Initial Findings From the 48-Month Analysis. 2025 AAIC. 4.Sabbagh M, et al. Real-World Use of Lecanemab in APOE ε4 Homozygotes and in Patients on Antithrombotic Therapy. 2025 AAIC. 5.Liu S, et al. Caregivers' perspectives on Lecanemab use for Alzheimer's disease: A national survey in China. Alzheimer's Dement. 2025. 21(9): e70680.

NEW YORK, Nov. 20, 2025 (GLOBE NEWSWIRE) -- Psyence Biomedical Ltd. (Nasdaq: PBM) (“Psyence BioMed” or the “Company”), a biopharmaceutical company advancing nature-derived psilocybin and ibogaine therapies for unmet mental health needs, today announced it had established a sustainable supply of high-potency iboga bark from trusted sourcing channels with deep experience in the iboga trade and treatment field through its strategic partner, PsyLabs. This is a significant achievement for the Company as it prepares for the clinical development of ibogaine for substance use disorders and validates its investment in PsyLabs. This collaboration with PsyLabs is an important step in securing a long-term supply of high-quality active pharmaceutical ingredients. PsyLabs’ ibogaine is fully GMP-compliant, ensuring it meets the rigorous standards required for clinical development. The first 50 kg has already been received and is now being processed into ibogaine HCL – the purified, pharmaceutical-grade form of ibogaine designed for precise dosing in clinical research – and into Total Alkaloid Extracts, which preserve the broader spectrum of iboga alkaloids found in the natural plant. Together, these products will be supplied to the legal research and treatment industries, supporting both standardized clinical trials and research into full-spectrum therapeutic approaches. Investing in a sustainable approach ensures that ibogaine and related alkaloids derived from Tabernanthe iboga and Voacanga africana are ethically sourced and pharmaceutical grade. By prioritizing quality, sustainability, and respect for the cultural traditions connected to these plants – including fair benefit-sharing with source communities – the Company is building a vertically integrated supply chain that meets the highest standards while supporting the long-term viability of this essential resource. “A reliable, ethically sourced supply of ibogaine is critical to our development pipeline,” said Jody Aufrichtig, Chief Executive Officer of Psyence BioMed. “This achievement not only strengthens our ability to advance our ibogaine-based clinical programs but also positions Psyence BioMed as a global leader in the emerging ibogaine sector. As international interest in ibogaine continues to accelerate, securing a sustainable and culturally respectful supply chain gives us a meaningful competitive advantage and reinforces our commitment to scientific rigor, responsible innovation, and the preservation of traditional knowledge.” "From soil to science, we will continue to ensure our ibogaine is not only the purest on the market, but the most ethically sourced," said Tony Budden, CEO of PsyLabs. "We’re building a new standard for what ethical psychedelic production can look like – where traditional knowledge holders are partners, not just suppliers." Today’s announcement advances Psyence BioMed – together with PsyLabs – toward a leading role in shaping the future of ibogaine development for substance use disorders and other urgent mental health needs. Learn more at www.psyencebiomed.com and on LinkedIn. About Psyence BioMed Psyence Biomedical Ltd. (Nasdaq: PBM) is one of the few multi-asset, vertically integrated biopharmaceutical companies specializing in psychedelic-based therapeutics. It is the first life sciences biotechnology company focused on developing nature-derived (non-synthetic) psilocybin and ibogaine-based psychedelic medicine to be listed on Nasdaq. We are dedicated to addressing unmet mental health needs, particularly in palliative care. The name ‘Psyence’ merges ‘psychedelics’ and ‘science,’ reflecting the company’s commitment to an evidence-based approach in developing safe, effective, and FDA-approved nature-derived psychedelic treatments for a broad range of mental health disorders. About PsyLabs PsyLabs is a psychedelic Active Pharmaceutical Ingredient (API) development company, federally licensed to cultivate, extract, and export psilocybin mushrooms and other psychedelic compounds including psilocin, mescaline, ibogaine, and dimethyltryptamine (DMT) to legal medical and research markets. The company has successfully exported psilocybin products to Canada, the UK, Portugal, and Slovenia, and supplies purified extracts to its UK-based CMO partner. PsyLabs operates from an ISO 22000-certified facility audited by the British Standards Institution, ensuring the highest standards of safety and traceability. With a focus on natural compound purification, regulatory support, and global distribution, PsyLabs is expanding its product pipeline to include ibogaine and other next-generation psychedelics.www.psylabs.life Contact Information for Psyence Biomedical Ltd.Email: ir@psyencebiomed.com Media Inquiries: media@psyencebiomed.com General Information: info@psyencebiomed.com Phone: +1 416-477-1708 Investor Contact:Michael KyddInvestor Relations Advisormichael@psyencebiomed.com Forward Looking Statements This communication contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about future financial and operating results, our plans, objectives, expectations, and intentions with respect to future operations, products and services; and other statements identified by words such as “will likely result,” “are expected to,” “will continue,” “is anticipated,” “estimated,” “believe,” “intend,” “plan,” “projection,” “outlook” or words of similar meaning. Forward-looking statements in this communication include statements regarding the advancement of the clinical development pipeline of ibogaine and the quality of the ibogaine derived or containing products under development. These forward-looking statements are based on a number of assumptions, including the assumption that all parties involved in the ibogaine supply chain will retain such valid permits and licenses as may be required to carry out their activities and that the demand for psychedelic-containing products and related therapy will continue to increase. There can be no assurance that the Company will continue to maintain compliance with Nasdaq’s continued listing requirements. There are numerous risks and uncertainties that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, among others: (i) delays in the execution of the Company's drug development and clinical trial pipeline; (ii) the ability of Psyence BioMed to maintain the listing of its common shares and warrants on Nasdaq; (iii) volatility in the price of the securities of Psyence BioMed due to a variety of factors, including the recent share consolidation, changes in the competitive and highly regulated industries in which Psyence BioMed operates, variations in performance across competitors, changes in laws and regulations affecting Psyence BioMed’s business and changes in Psyence BioMed’s capital structure. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of the Company’s final prospectus (File No. 333-298285) filed with the Securities and Exchange Commission (the “SEC”) on November 3, 2025 and other documents filed by Psyence BioMed from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Actual results and future events could differ materially from those anticipated in such statements. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Except as required by law, Psyence BioMed does not intend to update these forward-looking statements. The Company does not make any medical, treatment or health benefit claims about its proposed products. The U.S. Food and Drug Administration, Health Canada or other similar regulatory authorities have not evaluated claims regarding psilocybin, psilocybin analogues, or other psychedelic compounds or nutraceutical products. The efficacy of such products has not been confirmed by authorized clinical research. There is no assurance that the use of psilocybin, psilocybin analogues, or other psychedelic compounds or nutraceuticals can diagnose, treat, cure or prevent any disease or condition. Vigorous scientific research and clinical trials are needed. The Company has not conducted clinical trials for the use of the proposed products. Any references to quality, consistency, efficacy, and safety of potential products do not imply that the Company has verified such in clinical trials or that the Company will complete such trials. If the Company cannot obtain the approvals or research necessary to commercialize its business, it may have a material adverse effect on the Company’s performance and operations.