Ferumoxytol

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

Zahid Hussain|Rusel Mohammed Dhaidan|Ahmad Alshammari|Farida Ahmed Fikry|Hnin Ei Thu阿联酋沙迦大学药学院药学与制药技术系，沙迦27272摘要乳腺癌仍然是女性中最常见的恶性肿瘤，也是癌症相关死亡的主要原因，这凸显了需要超越传统诊断和治疗方法的创新策略。氧化铁纳米颗粒（IONPs）因其超顺磁性、生物相容性以及高度可调的物理化学性质（包括核心尺寸、结晶度、表面化学和多功能涂层）而成为一种多功能纳米平台。本文深入探讨了基于IONPs的乳腺癌诊疗技术的最新进展，特别关注药物递送、磁热疗法、光热疗法以及结合成像、靶向和组合治疗模式的集成平台。经过合理设计的IONPs通过配体介导的摄取、pH值或酶响应的药物释放，以及与化疗、基因疗法或免疫疗法的联合使用，能够提高肿瘤特异性和治疗效果。同时，其固有的磁性质支持通过MRI和互补成像技术进行实时治疗监测，进一步增强了其作为真正诊疗工具的价值。尽管取得了这些进展，但临床转化仍受到安全性考虑、长期组织滞留、免疫原性表面涂层以及在监管框架下可重复大规模生产的挑战的限制。令人鼓舞的是，新兴的临床研究表明了MRI引导下的热疗和基于IONPs的多功能系统的可行性。展望未来，人工智能引导的设计、免疫工程和生物标志物驱动的个性化预计将解决当前的限制并加速临床应用。总体而言，IONPs在乳腺癌管理中代表了一个充满希望的前沿，提供了基于材料的解决方案，将诊断和治疗结合在精准肿瘤学的范式中。引言乳腺癌（BC）仍然是全球女性中最常被诊断出的恶性肿瘤，也是癌症相关死亡的主要原因。2022年，新诊断出的病例超过230万例，占所有女性癌症病例的近三分之一，全球约有67万名女性因此丧生。尽管由于筛查技术的进步、分子靶向治疗和综合护理模式的实施，高收入地区的死亡率稳步下降，但全球发病率和死亡率仍在上升——尤其是在早期检测和先进治疗手段有限的低收入和中等收入国家。预后严重依赖于疾病阶段：局部期患者的五年生存率超过90%，但晚期和转移性疾病的生存率仍很低，低于30%。这些差异突显了现代肿瘤学在早期疾病方面的成功，同时也表明针对侵袭性和晚期癌症的有效策略仍然存在不足。当前的诊断方法（包括乳腺X线摄影、超声、磁共振成像（MRI）、正电子发射断层扫描（PET）和组织病理学活检）已经显著改善了早期检测和指导治疗选择。然而，这些方法仍存在局限性：乳腺X线摄影在乳腺组织密集的女性中灵敏度较低，超声依赖操作者技术，PET/MRI成本高昂且并非普遍可用。虽然活检具有决定性，但具有侵入性，可能存在采样偏差，并不适合长期监测。同样，手术、放疗、化疗、激素治疗和靶向生物制剂等治疗方法延长了生存期并提高了生活质量，但它们受到全身毒性、内在和获得性耐药性、肿瘤异质性以及在三阴性乳腺癌（TNBC）等侵袭性亚型中疗效不佳的限制。这些挑战强调了开发能够提高诊断精度、指导个性化治疗并减少脱靶毒性的创新技术的紧迫性。纳米技术通过利用纳米级的物理化学性质来改进疾病检测、药物递送和治疗选择性，成为肿瘤学领域的一个变革性前沿。在各种纳米材料中，氧化铁纳米颗粒（IONPs）因其固有的超顺磁性、良好的生物相容性和高表面积与体积比而具有巨大潜力，这使得它们可以进行多种功能化修饰。它们的磁性质能够增强MRI对比度，而通过聚合物、靶向配体或肽进行定制的表面工程则有助于主动定位肿瘤。除了诊断成像外，IONPs还作为药物递送、基因治疗和磁诱导热疗或光热消融的多功能平台。这种结合诊断和治疗的双重能力体现了“诊疗一体化”的概念，为精准肿瘤学提供了综合方法。本文深入探讨了IONPs在乳腺癌成像和治疗中的应用进展。与主要列举临床前结果的以往综述不同，我们强调了机制机制、功能化策略的比较评估，以及与毒性、生物分布、生产可扩展性和监管批准相关的转化挑战。我们还强调了IONPs与人工智能驱动的成像分析、免疫疗法和组合纳米医学等前沿策略之间的协同作用。通过整合临床前模型和新兴临床试验的证据，本文旨在明确IONPs作为下一代乳腺癌诊疗工具的机会、局限性和未来发展方向。IONPs：性质与生物医学相关性由于其独特的物理化学和磁性质，IONPs成为生物医学领域中最通用且临床相关性最强的纳米材料之一。在纳米尺度上，IONPs表现出超顺磁性，即在外部磁场作用下快速磁化并在磁场去除后完全失去剩磁的现象。这一性质防止了纳米颗粒聚集，实现了对纳米颗粒活动的精确空间和时间控制。传统成像的局限性乳腺癌的诊断仍然依赖于乳腺X线摄影、超声、MRI、CT、PET和组织活检。乳腺X线摄影是标准的筛查方法，但在乳腺组织密集的情况下灵敏度较低，导致假阴性结果和不必要的复检；超声在乳腺组织密集的情况下有一定效果，但特异性有限；MRI具有极高的灵敏度，但成本高昂且耗时较长，且并非普遍可用；PET/CT虽然有助于分期，但会带来电离辐射；而活检虽然具有决定性，但具有侵入性。针对乳腺癌诊疗的IONPs亚型特异性设计乳腺癌是一种生物学上异质性很强的疾病，包含多种分子亚型——主要是激素受体阳性（ER/PR+）、人表皮生长因子受体2阳性（HER2+）和三阴性乳腺癌（TNBC）——每种亚型都有不同的受体表达模式、肿瘤微环境（TME）特征和治疗敏感性。因此，IONPs的诊疗效果强烈依赖于合理的、考虑亚型差异的设计。IONPs的临床进展与其他许多无机纳米材料相比，IONPs在临床转化方面取得了更大进展，已有几种制剂被用于临床成像或治疗。早期获得批准的产品如Feridex?（铁氧化物）和Resovist?（铁羧酸盐）证明了IONPs作为磁共振成像（MRI）对比剂的可行性，而Feraheme?（铁氧醇）虽然最初被批准用于治疗缺铁性贫血，但后来也被广泛重新用于其他用途。关键讨论与未来展望IONPs因其独特的磁性质、生物相容性和多功能工程能力，成为癌症诊疗中最通用的纳米平台之一，尤其是在乳腺癌领域。它们的主要优势在于能够作为多功能制剂，将药物递送、磁热疗法、光热疗法和成像技术（MRI、CT、荧光或SPECT）整合到一个平台上。结论IONPs在乳腺癌管理中代表了变革性的前沿，能够将靶向药物递送、磁热疗法、光热消融和先进成像集成到一个多功能纳米平台上。在当前的纳米诊疗平台中，IONPs独特地结合了成像、治疗和磁控制功能，这使它们区别于脂质体、金纳米颗粒和聚合物系统。其可调的物理化学性质使其具有独特优势。CRediT作者贡献声明Zahid Hussain：撰写——综述与编辑、初稿撰写、监督、软件使用、资源管理、数据分析、概念化。Ahmad Alshammari：初稿撰写、方法学设计、数据管理。Rusel Mohammed Dhaidan：初稿撰写、方法学设计、数据管理。Hnin Ei Thu：综述与编辑、可视化处理、软件使用、资源管理、数据分析。Farida Ahmed Fikry：初稿撰写。未引用参考文献116.; 117.; 118.; 119.; 120.; 121.利益冲突作者声明在本研究中不存在利益冲突。利益冲突声明作者声明没有已知的财务利益或个人关系可能影响本文的研究结果。致谢作者感谢沙迦大学、阿联酋以及医学与健康科学研究所（RIMHS）在完成本综述项目过程中提供的宝贵支持。