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 每年流感流行都会袭击数百万人，导致多达 50 万人死亡。死亡大部分由 季节性流感病毒<0.03%，但在年轻人和老年人群中死亡率很高。 当一种新的致病性流感毒株进入人群时，大流行可能会导致数千万人死亡 预计造成的负面经济影响超过 1500 亿美元。由于药效不完全 目前的疫苗、有效的药物治疗是必要的。目前，流感治疗仅在一定程度上 有效，并且一些流感毒株对目前市售的治疗药物金刚烷类和 神经氨酸酶抑制剂达菲®。然而，虽然扎那米韦（ZAN，Relenza®）仍然具有高度活性 奥司他韦耐药的流感病毒株，其治疗效果受到其给药途径的严重限制， 口服吸入，这使得它不适合呼吸系统受损的患者。所以， 正如我们在此提议的那样，为 ZAN 开发一种新颖的交付替代方案，有望解决一个重大的未满足问题 医疗需要。 透皮给药系统比其他给药系统有许多改进。药物直接进入 体循环、规避吸收和口服给药典型的首过障碍。它避免了皮肤 通过注射器针头穿刺，消除疼痛和患者就诊。 ZAN 的透皮给药可以 在流感爆发期间能够接触到大量患者，这一点尤为重要 鉴于持续的 COVID-19 大流行期间增加的风险。而ZAN本身无法穿过人体皮肤 微阵列贴片 (MAP) - 增强的透皮递送是一种优雅、高效、 以及增加许多药物（包括 ZAN）皮肤渗透性的无痛方法。我们的新型药物装置 组合产品 TSR-066 由可膨胀微针阵列组成，可持续输送 ZAN 从特殊配制的储液罐中提取超过 5 天。该快速通道 SBIR 提案将支持优化 MAP 重点关注涂抹器组件和后续 I 期临床用品的制造 学习。我们已与 FDA 就开启 IND 所需的临床前研究达成一致，因为 以及 I 期临床开发计划和 505(b)2 监管策略。除了 此处提出的实验工作，我们正在为 TSR-066 开发强大的 IP 扩展策略，以及 未来的候选产品将受益于 MAP 交付。 这项工作的最终结果将是为 ZAN 提供一种新颖的透皮给药方法，这将扩大其覆盖范围 分为 Relenza® 禁忌的患者组，并允许对两者进行简单的 ZAN 给药 流感的治疗和预防。我们组建了一个由专家顾问和合作者组成的团队，以确保 顺利完成本研究计划。