EnLAmB - Enabling global access to affordable generic liposomal amphotericin B injectable formulations via advanced manufacturing technology

EnLAmB - 通过先进的制造技术，使全球能够获得负担得起的通用脂质体两性霉素 B 注射制剂

• 批准号: MR/X014010/1
• 负责人: Yiwei Tian
• 金额: $ 105.44万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX014010%2F1
• 关键词: EnLAmB; Enabling; global; access; affordable

Over 1 billion people are currently affected by Neglected Tropical Diseases (NTDs), resulting in half a million deaths and up to 57 million disability-adjusted life years lost annually. Within the NTD population, many deaths are also attributed to HIV-associated fungal infections, such as cryptococcal meningitis (CM), talaromycosis, and histoplasmosis. Recently, the burden of fungal infections was further deepened by COVID-associated pulmonary aspergillosis and mucormycosis. Liposomal amphotericin B (L-AmB)/AmBisome® has been the treatment of choice for these opportunistic fungal infections, offering superior safety and efficacy for immunocompromised patients. However, since the approval of L-AmB in 1997, the availability and affordability of this essential medicine remain a major challenge in low/middle-income countries (LIMCs). Only 22 of the 116 epidemic countries have L-AmB registered and available, representing an underserved population of over 2.8 billion. Access to the L-AmB in these countries has heavily relied on the donations made by the only manufacturer of AmBisome®, and private treatment can cost as high as £50,000 per patient. The lack of access to L-AmB at affordable prices is a public health crisis and represents a significant challenge to global health equity.Given the difficulties and high costs of new drug development and the current commercial and public health deficiencies in this field, it is more realistic and impactful to resolve the L-AmB global supply issues through the cheaper and scalable generic medicine approach. However, the current method for generic L-AmB manufacturing is costly and unscalable. We have developed a simple, cost-effective, scalable manufacturing technology for directly producing L-AmB. Our approach aims to transform the traditional 5-step complex process into a single-step continuous process, significantly reducing costs and increasing production efficiency. We plan to further develop this technology for generic L-AmB bioequivalence study in humans.

目前有超过 10 亿人受到被忽视的热带病 (NTD) 的影响，每年导致 50 万人死亡，并损失多达 5700 万的伤残调整生命年。在 NTD 人群中，许多死亡也是由艾滋病毒相关真菌感染引起的。 ，如隐球菌性脑膜炎（CM）、踝部真菌病和组织胞浆菌病，最近，与新冠肺炎相关的肺曲霉病和组织胞浆菌病进一步加重了真菌感染的负担。脂质体两性霉素 B (L-AmB)/AmBisome® 一直是这些机会性真菌感染的首选治疗方法，为免疫功能低下的患者提供了卓越的安全性和有效性，但自 1997 年 L-AmB 获得批准以来，其可用性和可负担性都受到了影响。这种基本药物的使用仍然是低/中等收入国家 (LIMC) 的一项重大挑战，在 116 个流行国家中，只有 22 个国家对 L-AmB 进行了注册和登记。这些国家有超过 28 亿人口无法获得 L-AmB 治疗，这在很大程度上依赖于唯一的 AmBisome® 制造商的捐赠，每位患者的私人治疗费用高达 50,000 英镑。以可承受的价格生产 L-AmB 是一场公共卫生危机，也是对全球卫生公平的重大挑战。考虑到新药开发的困难和高昂成本以及当前该领域商业和公共卫生方面的缺陷，更加现实和可行通过更便宜且可扩展的仿制药方法有效解决 L-AmB 全球供应问题。然而，目前的仿制药 L-AmB 制造方法成本高昂且无法扩展，我们开发了一种简单、经济高效、可扩展的制造技术。我们的方法旨在将传统的 5 步复杂工艺转变为单步连续工艺，从而显着降低成本并提高生产效率。我们计划进一步开发这项技术，用于人体通用 L-AmB 生物等效性研究。