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

目前有10多亿人受到被忽视的热带病的影响，每年造成50万人死亡和多达5700万个残疾调整生命年的损失。在NTD人群中，许多死亡也归因于与艾滋病毒相关的真菌感染，如隐球菌性脑膜炎(CM)、距菌病和组织胞浆菌病。最近，COVID相关性肺曲霉菌病和毛霉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®已成为治疗这些机会性真菌感染的首选药物，为免疫功能低下的患者提供了卓越的安全性和有效性。然而，自1997年L-AMB获得批准以来，这种基本药物的可获得性和可负担性仍然是低收入/中等收入国家的一大挑战。在116个流行国家中，只有22个国家登记并提供了L-AMB，这意味着有28多亿人口没有得到充分的服务。在这些国家，L-Amb的使用严重依赖AmBisome®唯一制造商的捐赠，私人治疗费用可能高达每位患者50,000 GB。无法以负担得起的价格获得L-AMB是一种公共卫生危机，对全球卫生公平构成了重大挑战。鉴于新药开发的困难和高昂的成本，以及该领域目前商业和公共卫生方面的不足，通过更便宜、可扩展的仿制药方法解决L-AMB的全球供应问题更现实、更有影响力。然而，目前用于非专利L-AMB制造的方法成本高且无法扩展。我们开发了一种简单、成本效益高、可扩展的制造技术，可以直接生产L-AMB。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，显著降低成本，提高生产效率。我们计划进一步开发这项技术，用于人体仿制L-AMB的生物等效性研究。

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.