Ferumoxytol

纳米技术曾被寄予厚望——2020年全球新确诊癌症病例1930万，死亡996万，每一串数字背后都是家庭崩塌的计量。当传统化疗药因为“敌我不分”而杀伤正常细胞时，科学家把目光投向纳米载体：能否把药物精准打包，送到肿瘤门口再释放？ 如今，近80种抗肿瘤纳米药物已进入临床阶段，16种获批上市，静脉、口服、瘤内注射三种给药方式齐头并进。然而，I期成功率94%、II期53%、III期仅18%的惨淡数据提醒人们：从实验室的“亮点”到患者的“救命药”，中间隔着一条深不见底的“死亡谷”。 1.1 ◉ 生物学屏障：五步递送步步惊心 静脉注射后，纳米粒要穿越血液循环→肿瘤蓄积→组织穿透→细胞内吞→胞内释放五道关口。任何一步效率低下，都会让前期努力付诸东流。 蛋白冠：血液里的白蛋白、补体、抗体像贴标签一样裹住纳米粒，改变其电荷、粒径与稳定性，“隐形”靶点瞬间变“失踪”。 MPS清道夫：肝脏、脾脏的巨噬细胞像垃圾桶一样把外来物迅速吞噬，“首过效应”让剂量还没抵达肿瘤就腰斩。 EPR失效：动物模型里风光无限的“增强渗透与滞留”效应，在人体常失约；肿瘤血管的“漏”与“堵”高度异质，同一个人左右肺的EPR参数都可能不同。 瘤内迷宫：高间隙液压、高细胞密度、致密基质像水泥一样阻挡纳米粒深入；尺寸稍大即遭遇“堵车”。 细胞内陷阱：溶酶体酸性环境与降解酶让包裹物“还没开工先被熔”，逃逸失败等于前功尽弃。 1.2 ◉ 临床安全：毒性黑天鹅为何频频出现 纳米载体改变药物体内分布后，肝、脾等正常组织意外“富集”，急性补体激活、溶血、氧化应激、线粒体损伤等毒性相继浮现。 20%患者因严重免疫相关不良反应导致I期试验终止——“有效”与“安全”两条红线同时踩线，才是临床试验的终点。传统毒性评价手段已跟不上纳米材料的复杂脚步，长期毒性、免疫原性、新型生物材料安全性仍是一片空白。 1.3 ◉ 物理化学异质性：放大生产“翻车现场” 纳米药物多组分、多步骤的构建方式，导致批次间粒径、电荷、包封率飘忽不定；放大生产一旦失控，小鼠里“神药”转眼变成“毒药”。 工业级生产必须把化学、制造与控制（CMC）指标写进“显微镜级”精度，才能保证患者用到的是“同一副牌”。 1.4 ◉ 动物模型：预言家的失声 缺乏“人味”的动物模型，让体外数据与体内疗效之间横亘一条莫比乌斯环。肿瘤微环境、血管结构、免疫组成的人兽差异，让看似有效的pre-clinic数据在临床惨遭打脸。 更糟的是转移模型稀缺——原位瘤里风光无限，一旦转移到肝肺就原形毕露；而转移才是癌症致死的主因。 2.1 ◉ 患者筛选：先问“谁能上车” 与其让不适合的患者当“小白鼠”，不如用分子影像或生物标志物提前“验明正身”。 主动靶向：如前列腺特异性膜抗原（PSMA）抗体偶联纳米粒，可通过免疫组化或PET/CT提前锁定“合格乘客”。 被动靶向：氧化铁纳米粒ferumoxytol已可借MRI预测肿瘤对伊立替康脂质体的“接收度”；MRI信号越高，后续疗效越好。 同载显像剂：64Cu标记脂质体PET成像可实时监测肿瘤蓄积，把“盲盒”变“透明盒”。 2.2 ◉ 模型药物：别让“错药”毁了前程 BIND-014在头颈癌II期失利，核心原因就是包载药物多柔比星与适应症错位。未来应更多考虑非传统药物： 高强度低毒性药物：Auristatins类萘胺衍生物游离态毒性大，纳米包载后疗效提升且全身耐受良好。 核酸大分子：siRNA、mRNA需要防降解并精准递送至APC；脂质体+聚合物复合物已把递送效率提高到90%以上。 蛋白药物靶向化：IL-2被脂质体包裹后循环时间延长、全身毒性锐减，为免疫治疗铺路。 2.3 ◉ 联合治疗：把单打独斗变成团队作战 单独伊立替康脂质体对胰腺癌OS并无优势，但联合化疗后显著延长生存；纳米药物可同时包载多种药物或生物制剂，实现“一箭多雕”。 克服递送屏障：氯沙坦降低TGF-β信号，松动基质；碳酸氢钠脂质体逆转肿瘤酸性微环境，双管齐下提高渗透。 携手免疫治疗：多柔比星+奥沙利铂诱导免疫原性细胞死亡（ICD），放大PD-1抑制剂疗效；白蛋白紫杉醇+抗CTLA-4在三阴乳癌里让ORR翻倍。 联合局部治疗：放疗增敏、超声微泡透化、热疗响应脂质体（Thermodox）与热疗同步，让局部控制率再上一个台阶。 3.1 ◉ 精准输送：从“撒网”到“导弹” 基础研究继续拆解递送路径上的每一道锁——蛋白冠组成、肿瘤血管通透性、胞外基质密度、间质液压……数据越详尽，靶向越精准。 红细胞膜、肿瘤细胞膜等仿生外壳延长循环时间；热响应、pH敏感化学键实现“到货即释放”；把“隐形战机”升级为“隐形导弹”。 3.2 ◉ 免疫调控：从“逃避免疫”到“激活免疫” 纳米载体不再只是“运货卡车”，而是免疫调节器： DC靶向：脂质体包载肿瘤抗原RNA，递送到脾脏DC，诱导中央记忆T细胞。 ICD放大器：顺铂+奥沙利铂双杀，让肿瘤细胞“亮红灯”，吸引免疫细胞吞噬。 免疫检查点上调剂：DOX脂质体联合PD-L1阻断，比单药提高疗效4倍以上。 纳米药把免疫治疗从“后装”变成“同装”，既减轻副作用又放大疗效。 3.3 ◉ 稳定性与可控释放：让药物“稳坐”到终点站 通过可裂解化学键或模块化前药设计，把药物永久锚定在载体上或按需断裂释放；酸敏、还原敏、酶敏、温度敏的多模式释放系统，让药物在正确的时间、正确的地点、以正确的剂量爆发。 同时减少突释与循环泄露，把全身毒性压到最低。 3.4 ◉ 局部给药：避开循环风暴 静脉之外还有多种路径： 瘤内注射凝胶：局部浓度高、全身暴露低，显著降低骨髓抑制。 皮下植入微球：缓释抗原递送，诱导持久免疫记忆。 胸腔/腹腔给药：针对胸腹水或转移灶，“少即是多”——小剂量直达病灶。 3.5 ◉ 简约化设计：少即是美 复杂配方带来指数级质量难题；把配方减到两三种核心成分，可显著降低CMC难度与生产成本。 单分子层包覆：用磷脂+聚乙二醇即可实现长效循环；减少抗原表位暴露。 模块化组装：通过点击化学把药物与载体按需拼接，批次间重复性提高到99%。 简约化让小试数据更容易放大到临床规模，降低企业试错成本。 3.6 ◉ 新制造技术：把实验室搬进工厂 微流控芯片可一键生成单分散脂质体；非浸润模板微印制技术把氟碳乳液做成模具，印出形貌均一的金属或无机纳米粒；3D打印类器官芯片让异种移植模型长出患者自己的肿瘤微环境——研发周期从月级缩短到周级甚至日级。规模化生产的瓶颈正在被逐个击碎。 3.7 ◉ 体内外模型升级：让小鼠更像人 人源化肿瘤异种移植（PDX）、类器官芯片、3D打印活体胶质母细胞瘤模型……正成为新一代“预测神器”。 它们不仅能复现患者突变谱，还能实时监测药物渗透曲线；提前筛掉无效配方，把浪费留在实验阶段而非临床阶段。 只有约0.7%的注射剂量能真正抵达肿瘤组织；其余99.3%在循环里或被清除或被降解。找到这0.7%的秘密，是下一代纳米制剂的核心使命。 基础研究继续拆解每一步递送障碍； 临床研究坚持标准化筛选与联合策略； 制造技术迭代升级规模化一致性生产能力； 政策指南逐步完善CMC与安全性评估细则； AI、单细胞测序等新技术为数据赋能提速——五力齐发，才能把实验室里的亮点真正变成患者床头的救命稻草。 当更多安全、高效、可规模化的纳米抗癌药冲破死亡谷，“精准医疗+纳米递送”就不再是口号，而是每一位癌症患者的日常希望。

Ferabright is the first and only iron-based contrast agent for MRI in the brain Woburn, MA — February 26, 2026 — Azurity Pharmaceuticals, Inc. announced today that FerabrightTM (ferumoxytol injection) is now available in the U.S. Ferabright is the first and only iron-based contrast agent indicated for magnetic resonance imaging (MRI) of the brain in adults with known or suspected malignant neoplasms in the brain to visualize lesions with a disrupted blood-brain barrier.1 Ferabright was approved by the U.S. Food and Drug Administration (FDA) in October 2025. “Ferabright is an advanced superparamagnetic iron oxide nanoparticle contrast agent engineered for high relaxivity,” said Ronald Scarboro, CEO of Azurity Pharmaceuticals. “It significantly enhances image contrast and precision in brain tumor delineation compared to non-contrast MRI, offering clinicians a new tool for diagnostic imaging and improved patient care.” In a clinical trial, Ferabright-enhanced MRI significantly improved visualization of primary and secondary brain neoplasms compared with pre-contrast imaging.1 In addition to improved imaging, Ferabright offers an extended imaging window due to its long half-life.1 The relatively large molecular size of Ferabright means it remains intravascular during early time points (blood pool phase) with a plasma elimination half-life of ~21 hours.1,7,9 Brain tumor enhancement is best seen in delayed-phase MRI, when contrast enhancement marks blood-brain barrier breakdown and macrophage uptake.1,2,7,9,10 As an iron-based agent, Ferabright is processed through the body’s natural iron metabolism pathways,3,6,7 potentially reducing concerns related to long-term tissue retention associated with other contrast agents.2,8 And unlike many other agents, Ferabright is a contrast alternative for patients with renal insufficiency and other gadolinium contraindications,2,3,4 enabling access to contrast-enhanced MRI while reducing exposure to heavy metals found in other contrast agents.5 Using an iron‑based contrast agent may also support more environmentally sustainable imaging practices by reducing contrast‑related emissions.11,12,13,14 Azurity Pharmaceuticals acknowledges the invaluable contributions of the Oregon Health & Science University (OHSU) team and the patients who participated in the foundational research, with special recognition to the late Edward Neuwelt, MD, professor and lead investigator in OHSU’s Department of Neurology, whose pioneering work played a critical role in advancing Ferabright toward FDA authorization. “Ferumoxytol expands our MRI toolkit and provides an option for patients who are either contraindicated for or decline gadolinium,” said Csanad Varallyay, MD, PhD, Neuroradiologist based in Portland, Oregon, with longstanding research experience in ferumoxytol-enhanced MRI. Ferabright will be supplied in single-dose vials of 300 mg elemental iron per 10 mL (30 mg/mL) and 510 mg elemental iron per 17 mL (30 mg/mL) for intravenous infusion over at least 15 minutes.1 Ferabright is contraindicated in patients with known hypersensitivity to ferumoxytol, any of Ferabright’s components, or any other intravenous iron products. Reactions have included anaphylaxis.1 IMPORTANT SAFETY INFORMATION FERABRIGHTTM (ferumoxytol injection), for intravenous use FERABRIGHT is indicated for magnetic resonance imaging (MRI) of the brain in adults with known or suspected malignant neoplasms in the brain to visualize lesions with a disrupted blood-brain barrier. WARNING: ANAPHYLAXIS AND OTHER SERIOUS HYPERSENSITIVITY REACTIONS Fatal and serious hypersensitivity reactions, including anaphylaxis, have occurred in patients receiving ferumoxytol products that contain the same active ingredient as FERABRIGHT. Initial signs may include hypotension, syncope, unresponsiveness, and cardiac/cardiorespiratory arrest. Hypersensitivity reactions have occurred even in patients who previously tolerated ferumoxytol. Only administer FERABRIGHT as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Observe for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following FERABRIGHT infusion including monitoring of blood pressure and pulse during and after FERABRIGHT administration [see Warnings and Precautions (5.1)]. ADDITIONAL IMPORTANT SAFETY INFORMATION Contraindications FERABRIGHT is contraindicated in patients with known hypersensitivity to ferumoxytol, any of FERABRIGHT’s components, or any other intravenous iron products. Reactions have included anaphylaxis [see Warnings and Precautions (5.1)]. Warnings and Precautions Anaphylaxis and Other Serious Hypersensitivity Reactions: Fatal and serious hypersensitivity reactions, including anaphylaxis presenting with cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness, have occurred in patients receiving ferumoxytol products, which contain the same active ingredient as FERABRIGHT. Other adverse reactions potentially associated with hypersensitivity have occurred, including pruritus, rash, urticaria, and wheezing. These reactions have occurred in patients who had no prior exposure to ferumoxytol as well as in patients who previously tolerated ferumoxytol. Patients with a history of multiple drug allergies may have a greater risk of anaphylaxis with FERABRIGHT. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of ferumoxytol including FERABRIGHT may have more severe outcomes. Carefully consider the potential risks and benefits before administering FERABRIGHT to these patients. FERABRIGHT is contraindicated in patients with known hypersensitivity to ferumoxytol, any of FERABRIGHT’s components, or any other intravenous iron products [see Contraindications (4)]. Only administer FERABRIGHT as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after FERABRIGHT administration for at least 30 minutes and until clinically stable following completion of infusion. Allow at least 30 minutes after FERABRIGHT infusion for administration of any other medications that may cause serious hypersensitivity reactions or hypotension [see Dosage and Administration (2.1)]. In a clinical study in patients with iron deficiency anemia (IDA) (FERABRIGHT is not approved to treat IDA), regardless of etiology, hypersensitivity reactions were reported in 0.4% (4/997) of patients administered ferumoxytol as an intravenous infusion over at least 15 minutes. These included one patient with severe hypersensitivity reaction and three patients with moderate hypersensitivity reactions. In clinical studies predominantly in patients with IDA and chronic kidney disease (CKD) (FERABRIGHT is not approved to treat IDA or CKD), serious hypersensitivity reactions were reported in 0.2% (4/1,806) of patients administered ferumoxytol as a rapid intravenous injection (not an approved method of administration for FERABRIGHT). Other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria, or wheezing) were reported in 3.5% (63/1,806) of these patients. In postmarketing experience with ferumoxytol, fatal and serious anaphylactic type reactions presenting with cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported [see Adverse Reactions (6.2)]. Hypotension: FERABRIGHT may cause clinically significant hypotension. Monitor patients for signs and symptoms of hypotension following FERABRIGHT administration [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. In a clinical study in patients with IDA (FERABRIGHT is not approved to treat IDA), moderate hypotension was reported in 0.2% (2/997) of patients administered ferumoxytol as an intravenous infusion over 15 minutes. In clinical studies in patients with IDA and CKD (FERABRIGHT is not approved to treat IDA or CKD), hypotension was reported in 1.9% (35/1,806) of patients, including three patients with serious hypotensive reactions, who were administered ferumoxytol as a rapid intravenous injection (not an approved method of administration for FERABRIGHT). Hypotension has also been reported in postmarketing experience [see Adverse Reactions (6.2)]. Iron Overload: Use of FERABRIGHT can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Avoid use of FERABRIGHT in patients with iron overload. Magnetic Resonance Imaging Test Interference: Administration of FERABRIGHT may transiently affect the diagnostic ability of MRI. Conduct anticipated MRI studies (other than the intended FERABRIGHT brain imaging) prior to the administration of FERABRIGHT. Alteration of MRI studies may persist for up to 3 months following the FERABRIGHT dose. If MRI is required within 3 months after FERABRIGHT administration, use T1- or proton density-weighted pulse sequences to minimize the FERABRIGHT effects. MRI imaging using T2-weighted pulse sequences should not be performed earlier than 4 weeks after the administration of FERABRIGHT. Maximum alteration of vascular MRI signal is evident for 1 to 2 days following FERABRIGHT administration [see Clinical Pharmacology (12.3)]. FERABRIGHT will not interfere with X-ray, computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), planar nuclear medicine imaging, or ultrasound. Differences in Magnetic Resonance Imaging Appearance Compared to Gadolinium-Based Contrast: MRI obtained with FERABRIGHT may demonstrate different size, intensity, and pattern of contrast signal in lesions compared to images obtained with gadolinium-based contrast [see Clinical Studies (14)]. Be aware of the potentially limited interpretability of changes in lesion contrast appearance if prior images were not obtained with FERABRIGHT. Adverse Reactions The most common adverse reactions (≥0.65%) are nausea, pruritus, constipation, headache, diarrhea, increased blood pressure, bleeding, hyperpigmentation, vein injury, taste alteration, burning/tingling sensation with injection, red sclera, allergic rhinitis, back pain, vomiting, and increased ALT. (6.1) Additional adverse reactions (≥1%) reported in clinical trials of patients with IDA or patients with IDA and CKD (using dosing regimens and indications not approved for FERABRIGHT), included dizziness, fatigue, peripheral edema, edema, abdominal pain, cough, pyrexia, dyspnea, and muscle spasm. Please note that FERABRIGHT is not approved to treat IDA or CKD and these dosing regimens are not approved for FERABRIGHT. These are not all the possible side effects of FERABRIGHT. Please see Adverse Reactions (6) in the Prescribing Information for a full list. The Important Safety Information does not include all the information needed to use FERABRIGHT safely and effectively. For more information and full Prescribing Information please visit www.Ferabright.com. To Report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch PP-FRB-5398-US-EN-v1 10/25 References Ferabright [package insert]. Woburn, MA: Azurity Pharmaceuticals, Inc; 2025. American College of Radiology. ACR Manual on Contrast Media 2025. Accessed October 19, 2025. https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Contrast-Manual Toth GB, Varallyay CG, Horvath A, et al. Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Kidney Int. 2017;92(1):47-66. Adams LC, Jayapal P, Ramasamy SK, et al. Ferumoxytol-enhanced MRI in children and young adults: state of the art. AJR Am J Roentgenol. 2023;220(4):590-603. Finn JP, Nguyen KL, Hu P. Ferumoxytol vs. gadolinium agents for contrast-enhanced MRI: thoughts on evolving indications, risks, and benefits. J Magn Reson Imaging. 2017;46(3):919-923. Daldrup-Link HE, Theruvath AJ, Rashidi A, et al. How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. Pediatr Radiol. 2022;52(2):354-366. Yagmurlu B, Hamilton BE, Szidonya L, Barajas RF, Iv M. ferumoxytol-enhanced mri in brain tumor imaging. Adv Clin Radiol. 2024;6(1):175-186.American College of Radiology. ACR Manual on Contrast Media 2025. Accessed September 3, 2025. https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Contrast-Manual FDA Drug Safety Communication: FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings. US Food and Drug Administration. Published May 16, 2018. Accessed September 3, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body Hamilton BE, Nesbit GM, Dosa E, et al. Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging. AJR Am J Roentgenol. 2011;197(4):981-988. McConnell HL, Schwartz DL, Richardson BE, Woltjer RL, Muldoon LL, Neuwelt EA. Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific. Nanomedicine. 2016;12(6):1535-1542. Feraheme [prescribing information]. Waltham, MA: AMAG Pharmaceuticals, Inc; 2022. Dekker HM, Stroomberg GJ, Van der Molen AJ, Prokop M. Review of strategies to reduce the contamination of the water environment by gadolinium-based contrast agents. Insights Imaging. 2024;15(1):62. Brünjes R, Hofmann T. Anthropogenic gadolinium in freshwater and drinking water systems.Water Res. 2020;182:115966. Chazot A, Barrat JA, Gaha M, Jomaah R, Ognard J, Ben Salem D. Brain MRIs make up the bulk of the gadolinium footprint in medical imaging. J Neuroradiol. 2020;47(4):259-265. About Azurity Pharmaceuticals: Azurity Pharmaceuticals is a privately held global pharmaceutical company dedicated to addressing the critical and often invisible crisis facing overlooked patients by purposefully developing and tailoring innovative pharmaceutical solutions to meet their specific, unmet needs, which are often ignored by the broader industry. By reformulating, adapting, and developing new therapies that meet specialized patient needs, we are delivering treatment alternatives that solve issues impacting patients’ day-to-day lives. With a broad portfolio of more than 50 medicines across 10 therapeutic areas fueling our mission, Azurity has the agility and velocity to provide safe, quality therapies that are reliable and easy to use. For more information, visit www.azurity.com Media Contact media@azurity.com FERABRIGHTTM is distributed by Azurity Pharmaceuticals, Inc. © 2026 Azurity Pharmaceuticals. All rights Reserved. This is intended for viewership in U.S. only. This press release may contain forward-looking statements subject to risks and uncertainties; actual results may differ materially. PP-FRB-6730-US-EN-v2 2/26