SUPPORTING WHO ONCHOCERCIASIS ELIMINATION PROGRAMS: PROGRESSING A HIGHLY SENSITIVE AND ULTRA-SPECIFIC RAPID DIAGNOSTIC TEST TO COMMERCIALIZATION READINESS

项目摘要/摘要 世卫组织需要新的、高灵敏度和超特异性的侧向流动分析(LFA)来支持其消除 盘尾丝虫病，一种又称河盲症的疾病，影响着1800万人，另有2.18亿人存活 有感染这种疾病的风险。盘尾丝虫病是由大众药物管理局(MDA)抗击的。世界卫生组织批评 需要新的诊断测试来支持启动和停止MDA计划的决策，并于2021年发布 相应的期望目标产品配置文件(TPP)。最严格的TPP标准是，测试必须是 异常特异(≥99.8%)。 我们的非营利性姐妹公司热带疾病药物和诊断公司(DDTD)分别于2020年和2021年受聘于 全球卫生特别工作组(TFGH)和美国国际开发署(USAID)制定了一项 新的盘尾丝虫病快速诊断试验。我们成功地开发了一种由两个新的O. 在试纸上排列成两条不同测试线的螺旋体抗原。在一项独立评估中， 疾控中心发现，该检测的敏感性为89.6%(95%可信区间：79.2-95.2%，N=58)，特异性为100%(95%可信区间：99.95-100%， N=194)。这意味着我们的双向测试满足TPP的敏感性和特异性要求， 值得注意的是，即使在95%的可信区间下限，其特异度也为99.8%。鉴于这些数据，美国国际开发署已经 承诺提供资金，在现场对大约10,000名个体进行评估，这将是 由TFGH于2023年初进行。 鉴于这些令人兴奋的结果，与公共卫生的巨大相关性，以及已经获得的巨大势头 与主要参与者(USAID、CDC、TFGH)一起，我们现在正在向NIH申请直接到第二阶段的资金，以迅速 将该检测方法推向工业化和商业化。第二阶段资金将用于(1)优化 在卷轴对卷轴制造友好的模式下进行双链测试，并确保关键试剂的访问，(2)建立 强大的制造流程，注重最大限度地降低成本和最大限度地提高速度，具有SOP和QC 针对制造环境进行验证的协议，以及记录在我们的质量管理体系中的批次到批次再生性数据的数据； 以及(3)生产100‘000台设备(20,000台中的5批)，将捐赠给利益相关者(TFGH/美国国际开发署)，以 支持进一步的现场测试和快速启动测试采用。值得注意的是，上述利益相关者已经 赞助我们最初的(“第一阶段”)研究，因此，确保他们的最大回报将是既得利益的 通过促进所有下游活动进行投资，为我们的测试商业化提供了一条明确的途径。 我们尊敬地认为，像我们的新测试这样的一流工具将支持消除河流 失明是一种疾病，有2100万活跃病例和2.18亿高危人群，将解决一个未得到满足的需求 对全球公共卫生具有极其重要的意义。

PROJECT SUMMARY / ABSTRACT WHO needs new, highly sensitive and ultra-specific lateral flow assays (LFA) to support its endeavors to eliminate onchocerciasis, a disease also known as river blindness affecting 18 million people, with another 218 million living at risk of contracting the disease. Onchocerciasis is fought by mass drug administration (MDA). WHO critically needs new diagnostic tests to support decisions to start and stop MDA programs and released in 2021 the corresponding desired target product profiles (TPPs). The most stringent TPP criterion is that the test must be extraordinarily specific (≥ 99.8%). Our non-profit sister company Drugs & Diagnostics for Tropical Diseases (DDTD) was hired in 2020 and 2021 by the Task Force for Global Health (TFGH) and the US Agency for International Development (USAID) to develop a new rapid diagnostic test for onchocerciasis. We succeeded in developing an assay composed of two novel O. volvulus antigens that are arranged as two distinct test lines on the assay strip. In an independent evaluation, the CDC found the test to be 89.6% sensitive (95% CI: 79.2-95.2%, N=58) and 100% specific (95% CI: 99.95-100%, N=194). This means that our biplex test meets the sensitivity and specificity requirements of both TPPs and, remarkably, its specificity is >99.8% even at the lower bound 95% CI. In view of these data, USAID has already committed funding to evaluate the assay in the field on approximately 10,000 individuals, which will be conducted by the TFGH in early 2023. Given these exciting results, the massive relevance for public health, and the big momentum already garnered with key players (USAID, CDC, TFGH), we are now requesting Direct-to-Phase II funding from the NIH to swiftly progress the assay to manufacturing and commercialization. Phase II funding will be used to (1) optimize the biplex test in a reel-to-reel manufacturing-friendly mode, and to secure access to critical reagents, (2) establish a robust manufacturing process, with a focus on minimizing costs and maximizing speed, with SOPs and QC protocols validated for a manufacturing context, and data on lot-to-lot reproducibility data recorded in our QMS, and (3) produce 100’000 devices (in 5 lots of 20’000) that will be donated to the stakeholders (TFGH/USAID) to support further field testing and jump-start test adoption. It is noteworthy that said stakeholders have already sponsored our initial (“Phase I”) research, hence will have a vested interest in ensuring maximum return on their investment by facilitating all downstream activities necessary to provide a clear path to commercializing our test. We respectfully submit that a first-in-class tool, such as our new test, that will support the elimination of river blindness, a disease with 21 million active cases and 218 million at-risk individuals, will address an unmet need of paramount significance for global public health.