Teprotumumab-TRBW

◆ ◆ ◆ ◆Paul's Insight2025年5月5日-5月11日◆ ◆ ◆ ◆在过去一周（5月5日至11日），全球药事监管与行业机构动作频繁：美国FDA在“美国造”战略、海外“突袭式”检查与AI审评三大领域持续发力；美国药典USP发布年度药品短缺报告，揭示供应链隐忧；欧洲EMA启动疫苗安全审查、AI与数据五年规划，并就ATMP生产指南征求意见；英国MHRA批准甲状腺眼病新药和环保吸入器、提示囊性纤维化药物心理风险；国际协调会议ICH和行业组织PDA、ISPE则在指南培训、疫苗制造速度和数字化转型等方面提供指导和思考。美国FDA监管的“三驾马车”1. “美国造”重启：行政令与供应链安全5月5日，美国总统特朗普签署《促进国内关键药品生产的监管减负》行政命令，明确要求FDA与其他联邦机构简化审批流程、提高可预测性，同时对海外原料药生产加强监管并可能公开不合规设施名单，以削弱对外依赖、保障国家安全。行政令还指示EPA加速关键设施建设审批，旨在缩短通常需要五年甚至更长的生产线落地时间，以推动罗氏、诺华等制药巨头进一步在美投资。此外，政府考虑对进口关键药品及其活性成分实施关税，以平衡贸易逆差并迫使生产回流，但具体方案尚处于内部评估阶段。图：美国总统特朗普签署《促进国内关键药品生产的监管减负》行政命令https://www.whitehouse.gov/presidential-actions/2025/05/regulatory-relief-to-promote-domestic-production-of-critical-medicines/2. 突袭检查：消弭“双重标准”5月6日，FDA宣布扩大无预警检查在海外药品及食品生产厂的应用，把此前仅在试点国家（中国、印度）进行的项目推广至全球所有出口美国的相关设施，强调“海外企业不再享有提前通知的特权”。FDA局长Marty Makary指出，此举有助于与美国本土同等标准对标，防范供应链中可能存在的质量风险。图：FDA官宣“突袭”式检查机制https://www.fda.gov/news-events/press-announcements/fda-announces-expanded-use-unannounced-inspections-foreign-manufacturing-facilities3. AI赋能：审评流程“提速降本”5月8日，FDA发布新闻稿，宣布将在6月30日前在全机构内部署生成式AI辅助科学审评系统，目标是将原需三天的文本分析与文献检索任务压缩至数分钟，被誉为“游戏规则改变者。该系统由CDER的Jinzhong Liu副主任试点，结果显示审评效率提升逾90%，极大减轻专家负担，并可将更多精力投入到复杂临床与生物等关键问题的深入评估。未来，FDA还计划将AI工具扩展至药物安全监测和临床试验数据分析，以全面构建“智能监管”体系。 图：FDA宣布全面部署AI辅助审评系统https://content.govdelivery.com/accounts/USFDA/bulletins/3df85e7美国药典USP《年度药品短缺报告》核心洞见5月7日，美国药典委员会（USP）发布《年度药品短缺报告》，指出2024年总短缺案列从2023年的125例降至98例，但长期短缺（≥1年）仍占90%以上，平均持续时间从约3年增至4年以上，且无菌注射剂占短缺总量69%。报告强调，生产地域集中度、低价仿制药利润微薄、复杂制造与质量检验难度大等因素交织，导致行业缺乏应对外部冲击（自然灾害、地缘风险、政策调整）的缓冲空间。超过40种药品短缺已超三年，其中5种无菌注射剂（如硫酸阿托品、盐酸利多卡因等）短缺达十年以上；近三分之一的短缺口服固体药物单价低于1美元，44%的短缺注射剂售价低于5美元。USP副总裁Vimala Raghavendran呼吁，通过数据共享与可视化工具，促进上下游协同，探索可持续定价与采购模式，以确保质量、韧性与创新投资三者兼顾。图：美国药典委员会（USP）发布《年度药品短缺报告》https://www.usp.org/news/long-lasting-drug-shortages-drive-average-duration-higher-disrupting-patient-care美国PDA实现“100天疫苗使命”5月7日，美国注射剂协会PDA刊文阐述了流行病防备创新联盟（CEPI）“100天使命”（100 Days Mission）的背景、目标及其在化学、制造与控制（CMC）流程中推动技术创新的具体举措，旨在通过一系列前沿工艺和平台优化项目，将新发疫苗从病原体识别到紧急使用授权的时间大幅缩短，以提升全球对未来大规模疫情暴发的快速响应能力。2021年启动的“100天使命”旨在实现在今后疫情暴发时，从病原体基因序列发布起100天内完成疫苗初步授权及早期生产。PDA文章指出，COVID-19疫情期间疫苗在326天内获批，已展示了跨平台快速开发的潜能，但要真正缩短至100天，则需在制造环节进行深度革新。PDA强调，实现“100天使命”不仅需要技术突破，还需监管机构、制造商和供应链合作伙伴在预先批准流程、全球试验网络以及多区域生产能力上的协同，方能在未来疫情来袭时做到“既快又稳”。图：PDA撰文——加速疫苗供应，以应对疾病威胁的紧急用途https://www.pda.org/pda-letter-portal/home/full-article/the-need-for-manufacturing-speed欧盟EMA监管双擎驱动1.  Ixchiq疫苗安全审查5月7日，欧洲药品管理局EMA安全委员会（PRAC）针对Valneva基孔肯雅减毒活疫苗Ixchiq启动审查，因全球报告17例62–89岁接种者中出现严重不良事件（含2例死亡），建议在审查期间禁止65岁及以上人群接种，同时提醒免疫功能低下者慎用。此次审查基于临床研究数据主要来自65岁以下群体，监管机构将评估该疫苗风险收益平衡，并可能调整适应症和警示条款。图：EMA 开始审查 Ixchiq（基孔肯雅减毒活疫苗）https://www.ema.europa.eu/en/news/ema-starts-review-ixchiq-live-attenuated-chikungunya-vaccine2. AI与数据五年规划同日， EMA发布《2025–2028年药品监管中的数据与AI》工作计划，描绘了人用与兽用药品监管网络中数据互操作、质量管理与高级分析的路线图，并强调符合欧洲健康数据空间（EHDS）、互联欧洲法案与AI法案的安全伦理规范，为未来监管决策提供坚实技术支撑。该计划涵盖数据治理、资产目录、元数据标准与机器学习应用等多项重点任务，旨在缩短审批周期并提高监管透明度。图：欧盟发布AI战略，打造“未来药监”体系https://www.ema.europa.eu/en/news/ema-starts-review-ixchiq-live-attenuated-chikungunya-vaccine3. ATMP生产指南修订概念文件5月8日，EMA发布《ATMP专属GMP指南第IV部分修订概念文件》，提出将2023年新版无菌生产附录1新增要求纳入ATMP指南范畴，强调需独立评估新技术与风险管理发展，面向利益相关方开放公众咨询至7月8日。该举措有助于统一基因与细胞治疗产品的高风险制造标准，并促进企业在新技术采用时保持合规。图：欧盟GMP附录1拟纳入ATMP专属指南https://ec.europa.eu/eusurvey/runner/Concept_paper_part_IV_guidelilnes_GMP_for_ATMPs英国MHRA疗法创新与环保并进1. Teprotumumab获批：首个TED靶向疗法5月7日，MHRA批准Amgen的teprotumumab（Tepezza）用于中度至重度甲状腺眼病（TED）成人患者，填补英国在该自身免疫性疾病领域的治疗空白。该药在287例患者的四项III期试验中，每3周一次输注共8次，显著改善眼球突出与复视等症状，安全性可控。图：英国首个TED靶向疗法获批https://www.gov.uk/government/news/mhra-approves-teprotumumab-as-the-first-uk-treatment-for-adults-with-moderate-to-severe-thyroid-eye-disease-ted?2. Kaftrio心理副作用风险提示5月7日，MHRA发布药物安全更新，警示囊性纤维化三联疗法Kaftrio可能引发焦虑、抑郁、睡眠障碍等心理不良反应，截至2月25日累计300份黄卡报告，涵盖9391名患者；监管机构建议医护人员及早识别并干预相关症状。媒体报道，2024年实现年销售额超过100亿美元的药品合计达12款，这是其中一款。图：Kaftrio心理副作用风险提示https://www.gov.uk/drug-safety-update/kaftriov-ivacaftor-tezacaftor-elexacaftor-risk-of-psychological-side-effects3. 批准使用“更环保”推进剂的阿斯利康吸入器5月12日，MHRA批准阿斯利康Trixeo Aerosphere低碳推进剂版，将HFA-134a替换为近零GWP的HFO-1234ze(E)，预计2025年下半年在英上市。该举措支持英国COPD患者治疗需求，同时响应制药行业碳减排承诺，推动至2045年实现90%绝对排放减少目标。图：英国批准使用“更环保”推进剂的阿斯利康吸入器https://www.gov.uk/government/news/mhra-approves-worlds-first-low-carbon-version-of-copd-inhaler-trixeo-aerosphere国际ICH发布Q5A(R2)培训材料5月6日，ICH发布Q5A(R2)《源自人或动物细胞系的生物技术产品的病毒安全性评价》培训材料0–3模块，面向行业与监管机构详细阐释2023年修订要点，并通过案例辅助实施。图：ICH发布Q5A(R2) 培训材料https://www.ich.org/news/ich-q5r2-viral-safety-evaluation-biotechnology-products-derived-cell-line-human-or-animal?ISPE三部曲监测、数字化与Pharma 4.0™ISPE本周继续撰文，对其即将举行的2025 ISPE年会主题进行了介绍。1. 数字化路线图进展数字化转型已非生物制药行业的未来愿景，而是深刻改变制造与质量控制流程的现实力量。ISPE即将在2025年生物技术大会上，汇聚终端用户、解决方案提供商与咨询机构的经验分享，从六场数据驱动、实践导向的专题演讲中揭示行业在运营、分析、质量与合规等方面的最新进展与挑战。图：IPSE探讨数字化路线图https://ispe.org/pharmaceutical-engineering/ispeak/where-are-we-digital-road-map-find-out-2025-ispe-biotechnology2. Pharma 4.0™进程Pharma 4.0™代表制药行业的数字化与数据驱动转型，旨在通过引入先进技术与稳健数据解决方案，提升生产效率、柔性和合规性，从而更快、更可靠地将创新药物推向患者。ISPE年会上将设立ATMP、数字转型、运营卓越等五大分会，搭建对话平台，推动合规与创新协同发展。图：IPSE探讨Pharma 4.0https://ispe.org/pharmaceutical-engineering/ispeak/journey-pharma-40tm-are-we-there-yet结 语从简化审批到突袭检查，从AI加持到数据驱动，从安全审查到环境可持续，各方监管与行业机构正跨界协同，以应对复杂多变的全球医药挑战。展望未来，随着AI与大数据持续渗透监管决策，全球药事监管生态可能会将更加高效、透明与韧性，为保障药品质量安全及公众健康提供坚实支撑。END声明：本文仅代表作者个人观点，不代表任何组织及本公众号立场，如有不当之处，敬请指正。如需转载，请注明作者及来源：蒲公英Biopharma。活动推荐5月16日 | 线上 | VHP生物指示剂的应用5月15日-16日 | 线下 | 2025中国制药工程设备产业大会5月20日 | 线上 | “药品注册申报中的质量研究”系列课程—“显微拉曼技术在药物制剂逆向工程中的应用”5月22日 | 线下 | 2025中国无菌药品制造创新发展论坛5月28日 | 线上 | 计算机化系统合规高效管理分享6月25日 | 线下 | 2025 CPHI 生物药商业化生产与创新论坛——分论坛：抗体药物生产能力建设研讨会6月25日 | 线下 | 2025 CPHI 生命科学与技术创新发展论坛——论坛二：细胞药物质量控制法规与技术论坛

CAMBRIDGE, England--(BUSINESS WIRE)--Today, Amgen announced that the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for TEPEZZA® (teprotumumab) as the first therapy specifically licensed for the treatment of adult patients with moderate-to-severe Thyroid Eye Disease (TED). Affecting approximately 50,000 people in the UK,1 TED is a progressive and potentially vision-threatening condition, which can cause eye bulging, double vision, eye pain, redness and swelling.2 People living with TED often experience anxiety and depression, concerns about their facial appearance and a loss of confidence.3 This can impact their ability to work, socialise and maintain relationships.3,6 “The marketing authorisation for teprotumumab as the first therapy specifically licensed for Thyroid Eye Disease (TED) in the UK marks a step forward for the patient community,” said Dr Tony Patrikios, Executive Medical Director, Amgen UK & Ireland. “TED can negatively affect patients’ lives impacting vision, causing eye pain, making everyday tasks difficult and causing a loss of self-confidence. This authorisation introduces a new alternative treatment option and reinforces Amgen’s commitment to supporting eligible patients with serious, underserved conditions.” Teprotumumab’s marketing authorisation in the UK is supported by multiple clinical studies,5,7,8,9 including the Phase 3 clinical trial, OPTIC (n=83).5 Other clinical studies that supported the marketing authorisation in the UK include the TED01RV Phase 2 clinical study (n=88),7 the HZNP-TEP-403 Phase 4 clinical study (n=62),8 and the OPTIC-J Phase 3 study in Japan (n=54).9 In the OPTIC trial, teprotumumab demonstrated a statistically significant improvement in the primary endpoint, proptosis (eye bulging) responder rate at 24 weeks, with 83% (34/41) of patients demonstrating a reduction of at least 2mm compared to baseline, versus 10% (4/42) of patients treated with placebo (difference of 73%, 95% confidence interval, 59 to 88; P=<0.001]).5 “For adult patients living with Thyroid Eye Disease (TED), it can be challenging to receive a diagnosis and referral to specialist centres. TED is often mistaken for other more common conditions, which can be frustrating and distressing for patients. This may also lead to delays in receiving treatment. When patients are diagnosed with TED, they are currently faced with limited treatment options targeting ‘generalised inflammation’. These treatments do not specifically target the underlying cause and drivers of TED,” said Dr Jimmy Uddin, Consultant Ophthalmologist, Oculoplastic & Orbital Surgeon, Moorfields Eye Hospital and St George’s Hospital Medical School. “Teprotumumab offers eligible TED patients in the UK an important new treatment option.” The safety data for teprotumumab is based on multiple clinical studies.5,7,8,9 The most common side effects observed in clinical trials are muscle spasms (27.6%), diarrhoea (14.5%), hearing impairment (13.8%), alopecia (13.2%), hyperglycaemia (13.2%), fatigue (12.5%), nausea (10.5%), headache (10.5%), dry skin (9.9%), dysgeusia (8.6%), COVID-19 (6.6%), ear discomfort (6.6%) and nail disorder (5.9%).4 Amgen will work with the National Institute for Health and Care Excellence (NICE) to seek reimbursement of teprotumumab for all eligible patients. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Notes to Editors About Thyroid Eye Disease (TED) TED is a serious, progressive and potentially vision-threatening autoimmune disease.10 It often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signalling complex on cells within the retro-orbital space.11,12 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness.13,14 Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and double vision.2 About teprotumumab Teprotumumab is a monoclonal antibody that specifically targets and blocks the insulin-like growth factor-1 receptor (IGF-1R), which is thought to play a central role in the development of TED.15 It binds to the IGF-1R, preventing it from being activated and sending signals that lead to muscle and tissue expansion, as well as inflammation behind the eye.15 This can help reduce TED symptoms, such as proptosis (eye bulging).4,5 For further product information, please see the Summary of Product Characteristics, which will be available at: https://www.medicines.org.uk/emc About the Phase 3 OPTIC clinical trial A prospective, multi-centre randomised, double-blind, placebo-controlled, Phase 3 trial of the IGF-1R inhibitor teprotumumab or placebo in adults with Graves’ disease and active moderate-to-severe thyroid eye disease.5 83 patients between the ages of 18-80 were recruited and randomised 1:1 to receive 8 intravenous infusions of either teprotumumab or placebo. Infusions were administered every 3 weeks over 21 weeks, with a final clinical evaluation at week 24. The initial dose of teprotumumab was 10mg/kg, with each subsequent infusion dosed at 20mg/kg.5 The primary endpoint of the trial was proptosis response, defined as a reduction of at least 2mm in proptosis from baseline in the study eye without a corresponding increase of at least 2mm in the fellow (contra-lateral) eye at week 24.5 For more information on the OPTIC clinical trial go to: https://clinicaltrials.gov/study/NCT03298867. About Amgen UK Amgen’s mission is to serve patients. A biotechnology innovator since 1980, our science- based heritage is at the heart of everything we do. We remain on the cutting edge of innovation, using technology and human genetic data to push beyond what is known today. In the UK, Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. As a regional hub, we employ around 650 people in the UK and Ireland across our commercial, R&D and corporate functions. Committed to driving sustainable solutions that can adapt to an ever-evolving health system, we are proud to serve patients every day. For more information visit: https://www.amgen.co.uk/ References 1 British Thyroid Foundation. Thyroid eye disease. Available at: https://www.btf-thyroid.org/thyroid-eye-disease/1000. Last accessed: May 2025. 2 Royal National Institute of the Blind (RNIB). Thyroid eye disease. Available at: https://www.rnib.org.uk/your-eyes/eye-conditions-az/thyroid-eye-disease/#:~:text=It%20is%20well%20known%20that,be%20taking%2C%20such%20as%20steroids. Last accessed: May 2025. 3 Smith TJ, et al. How patients experience thyroid eye disease. Front. Endocrinol. 2023;9(14):1283374. 4 TEPEZZA (teprotumumab) Summary of Product Characteristics. Will be available at: https://www.medicines.org.uk/emc 5 Douglas RS, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020;382:341-352. 6 British Thyroid Foundation. Thyroid eye disease: patient leaflet. Available at: https://www.btf-thyroid.org/thyroid-eye-disease-leaflet#:~:text=You%20may%20also%20feel%20anger,both%20social%20and%20at%20work. Last accessed: May 2025. 7 Smith TJ, et al. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med 2017;376:1748-1761. 8 Douglas RS, et al. Efficacy and Safety of Teprotumumab in Patients with Thyroid Eye Disease of Long Duration and Low Disease Activity. JCEM 2024;109(1):25-235. 9 Hiromatsu Y, et al. A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patients. Lancet Reg Health West Pac. 2025;55:101464. 10 Ponto KA, et al. Quality of life and occupational disability in endocrine orbitopathy. Dtsch Arztebl Int. 2009;106(17):283-289. 11 Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257. 12 Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol. 2003;170:6348-6354. 13 McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO ) survey. Br J Ophthalmol. 2007;91:455-458. 14 Bartalena L, et al. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy. Eur J Endocrinol. 2021;185(4):G43-G67. 15 Patel A, et al. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281-288.