Novel Influenza Biodefense Therapeutic and Prophylactic

新型流感生物防御治疗和预防药物

• 批准号: 6844233
• 负责人: Jane Ryan
• 金额: $ 562.83万
• 依托单位: BIOTA SCIENTIFIC MANAGEMENT
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844233
• 关键词: antiviral agents; bioterrorism /chemical warfare; chemoprevention; clinical research; clinical trial phase I; cooperative study; disease outbreaks; dogs; dosage forms; drug administration rate /duration; drug screening /evaluation; enzyme inhibitors; exo alpha sialidase; human subject; human therapy evaluation; influenza; inhalation drug administration; laboratory rabbit; laboratory rat; microorganism disease chemotherapy; nonhuman therapy evaluation; patient oriented research; pharmacokinetics

DESCRIPTION (provided by applicant): The application aims to develop a novel Influenza neuraminidase inhibitor (NAI) for protection and treatment of those exposed to a deliberately released, highly pathogenic strain of Influenza virus. The antiviral drug would also have complementary value in the event of a natural pandemic. The drug will be administered using a nebulizer in a single dose for therapy and once a week for prophylaxis. Current therapies for lnfluenza, including vaccines, cannot provide such a practical and immediately available protection from the threat of a potentially lethal Influenza virus. Biota Holdings Ltd developed the first-in-class NAI drug, Relenza (tm), through a partnership with GlaxoSmithKline (GSK). Although Relenza is considered to be safe and is effective for all existing Influenza NA variants, it and other anti-Influenza drugs have features that are less than ideal for mass treatment/prophylaxis in the event of a bioterrorist attack. In particular, pharmacokinetic limitations require that existing drugs be administered repeatedly during the period of exposure or treatment, which presents challenges in supply and compliance during a biodefense or a pandemic situation. Biota in collaboration with Sankyo Co. Ltd. have identified a new class of Long Acting Neuraminidase Inhibitors (LANI), and have advanced a representative LANI compound (R-118958) through completion of a Phase I human clinical safety study demonstrating pharmacokinetics consistent with once weekly dosing. In this study the drug was delivered via a dry powder inhaler. For biodefense a nebulized delivery of the drug would be favored as it would allow long term storage of a very active drug substance in bulk form. Formulation for nebulized delivery is a well recognized practice, readily conducted by pharmacists and healthcare professionals and would allow timely delivery to a population exposed to a bioterror agent. This application aims to conduct the studies required for development of a convenient nebulized form of R-118958.

描述（由申请人提供）：申请旨在开发一种新型的流感神经氨酸酶抑制剂（NAI），以保护和治疗暴露于故意释放的，高度致病的流感病毒菌株的人。在天然大流行的情况下，抗病毒药物也将具有互补的价值。该药物将使用单剂量的雾化剂进行治疗，每周一次进行预防。包括疫苗在内的LNFLUENZA的当前疗法无法提供这种实际且立即可用的保护，以免受到潜在致命的流感病毒的威胁。 Biota Holdings Ltd通过与GlaxoSmithkline（GSK）的合作伙伴关系开发了第一类NAI药物Relenza（TM）。尽管Relenza被认为是安全的，并且对于所有现有的流感NA变体都是有效的，但IT和其他抗炎性药物的特征对于发生生物恐怖主义攻击而言的特征对于群众治疗/预防症的理想程度不足。特别是，药代动力学的限制要求在暴露或治疗期间反复使用现有药物，这在生物幻影或大流行状况期间对供应和依从性提出了挑战。 Biota与Sankyo Co. Ltd.合作确定了一类新的长作用神经氨酸酶抑制剂（LANI），并通过完成I期人类临床安全研究，展示了与每周剂量一致的药代动力学，并通过完成了I期人类临床安全研究来提高了代表性LANI化合物（R-118958）。在这项研究中，该药物是通过干粉吸入器输送的。对于Biodefense，将有利于雾化的药物递送，因为它可以长期存储以散装形式的非常活跃的药物。雾化交付的配方是一种公认​​的实践，很容易由药剂师和医疗保健专业人员进行，并将允许及时向接触生物疗法的人群交付。 该应用程序旨在进行开发便利的雾化形式R-118958所需的研究。