Novel, Self-Applied MicroArray Patch (MAP) of Zanamivir for Treatment of the Flu

用于治疗流感的新型扎那米韦自用微阵列贴片 (MAP)

• 批准号: 10761086
• 负责人: Elke Lipka
• 金额: $ 30万
• 依托单位: TSRL, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10761086
• 关键词: Achievement; Acute; Adamantane; Address; Agreement; COVID-19 pandemic; Cessation of life; Circulation; Clinical; Clinical Research; Communities; Development; Development Plans; Devices; Disease; Drug Kinetics; Effectiveness; Elderly; Ensure; Epidemic; Epithelium; Family suidae; Formulation; Funding; Future; Grant; Human; Influenza; Influenza prevention; Inhalation; Light; Liquid substance; Literature; Lung; Manufactured Supplies; Marketing; Medical; Methods; Miniature Swine; Modeling; Needles; Neuraminidase inhibitor; Oral; Oseltamivir; Pain; Painless; Pathogenicity; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase I Clinical Trials; Plasma; Population; Powder dose form; Publishing; Puncture procedure; Rattus; Recommendation; Reproducibility; Research; Resistance; Respiratory System; Risk; Route; Safety; Seasons; Self Administration; Site; Skin; Small Business Innovation Research Grant; Syringes; System; Therapeutic; Toxicology; Transdermal substance administration; Vaccination; Vaccines; Visit; Work; absorption; clinical development; design; economic impact; effective therapy; flu; improved; in vivo; influenza epidemic; influenza outbreak; influenza virus strain; influenzavirus; manufacture; mortality; novel; novel therapeutics; pandemic disease; patient population; pre-Investigational New Drug meeting; preclinical study; prevent; programs; prototype; resistant strain; respiratory; scale up; seasonal influenza; skin barrier; skin irritation; transmission process; treatment adherence; treatment duration; vaccine effectiveness; zanamivir

Abstract Yearly influenza epidemics strike millions of people, causing up to 500,000 deaths. Fatality caused by most seasonal influenza viruses is <0.03%, but with significant mortality in the young and the elderly populations. When a new pathogenic influenza strain enters the population, a pandemic could kill tens of millions of people with a negative economic impact estimated to be over 150 billion dollars. Due to the incomplete efficacy of the current vaccines, effective drug treatment is necessary. Presently, influenza treatment is only somewhat effective, and some influenza strains are resistant to the currently marketed therapeutics, adamantanes and the neuraminidase inhibitor Tamiflu®. However, while zanamivir (ZAN, Relenza®) remains highly active against oseltamivir-resistant influenza strains, its therapeutic impact is severely limited by its route of administration, via oral inhalation, which renders it unsuitable for patients with a compromised respiratory system. Therefore, development of a novel delivery alternative for ZAN as we propose here, is poised to address a significant unmet medical need. Transdermal drug delivery offers a number of improvements over other delivery systems. The drug directly enters the systemic circulation, circumventing absorption and first-pass barriers typical for oral delivery. It avoids skin puncture by syringe needles, eliminating pain and patient visits to a clinician. Transdermal delivery of ZAN could allow large numbers of patients to be reached during an influenza outbreak, which will be particularly important in light of the added risk during the ongoing COVID-19 pandemic. While ZAN itself cannot cross the human skin barrier at therapeutic rates, MicroArray Patch (MAP) - enhanced transdermal delivery is an elegant, efficient, and painless method for increasing the skin permeation of many drugs, including ZAN. Our novel drug-device combination product, TSR-066, consists of a swellable microneedle array, which will continuously deliver ZAN from a specially formulated reservoir over 5 days. This Fast-Track SBIR proposal will support optimization of the MAP with a focus on the applicator component and subsequent manufacturing of supplies for the Phase I clinical study. We have obtained agreement with the FDA on the preclinical studies needed in order to open the IND, as well as on the Phase I clinical development plans and the 505(b)2 regulatory strategy. In addition to the experimental work proposed here, we are developing a robust IP expansion strategy for TSR-066, as well as future product candidates that stand to benefit from MAP-enabled delivery. The end result of this work will be a novel, transdermal delivery approach for ZAN, which will expand its reach into patient groups for which Relenza® is contraindicated and allow for simple administration of ZAN for both treatment and prevention of the flu. We have assembled a team of expert advisors and collaborators to ensure successful completion of this research plan.

抽象的 每年影响流行病的人数数百万，造成多达500,000人死亡。大多数人造成的死亡 季节性影响病毒<0.03％，但年轻人和老年人的死亡率显着。 当新的病原影响力进入人群时，大流行可能会杀死数千万人 经济影响负面影响估计超过1500亿美元。由于不完整的效率 目前，影响者的治疗只是有些 有效，一些有影响力的人对当前销售的疗法，亚当坦和 神经氨酸酶抑制剂tamiflu®。但是，尽管Zanamivir（Zan，Relenza®）仍然高度活跃 抗oseltamivir抗性的影响力菌株，其治疗影响受到其管理途径的严重限制， 口服吸入，这使其不适合患有受损呼吸系统的患者。所以， 正如我们在这里提出的那样，开发了Zan的新型交付替代品，被毒死以解决重要的未得到满足 医疗需求。 透皮药物输送比其他输送系统提供了许多改进。该药物直接进入 全身循环，规避滥用滥用和典型的口服障碍。它避免了皮肤 注射针头穿刺，消除疼痛和患者对临床的看法。 Zan的透皮交付可以 允许在影响力爆发期间与大量患者联系，这将特别重要 鉴于正在进行的共同19-19大流行期间的风险。 Zan本身无法跨越人类皮肤 以治疗速率，微阵列补丁（地图） - 增强的透皮交付是一种优雅，高效， 和无痛的方法，可以增加包括ZAN在内的许多药物的皮肤渗透。我们的新型药物设备 组合产品TSR-066由可膨胀的微针阵列组成，该阵列将继续提供Zan 从5天内从专门配制的储层中进行。这个快速轨道SBIR提案将支持优化 地图，重点是涂抹器组件以及随后的I期临床用品制造 学习。我们已经就开放IND所需的临床前研究获得了与FDA的同意，因为 以及在第一阶段临床开发计划和505（b）2监管策略。除了 在这里提出的实验工作，我们正在为TSR-066制定强大的IP扩展策略，以及 未来的产品候选人将从支持地图的交付中受益。 这项工作的最终结果将是Zan的新颖，透皮交付方法，这将扩大其影响力 进入患者群体，禁忌RERENZA®，并允许双方简单地给予ZAN 治疗和预防流感。我们组建了一个专家顾问和合作者团队，以确保 成功完成了该研究计划。