School of Medicine, University of Nevada, Las Vegas (UNLV), Las Vegas, NV, 89154, USA.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA.
Alzheimers Res Ther. 2020 Aug 17;12(1):98. doi: 10.1186/s13195-020-00662-x.
Treatments are needed to address the growing prevalence of Alzheimer's disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes.
We assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020.
We identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov.
Drug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.
需要治疗方法来应对阿尔茨海默病（AD）的发病率不断上升的问题。自 2003 年以来，临床试验未能生产出任何获得美国食品和药物管理局（FDA）批准的 AD 药物，而药物开发过程既耗时又昂贵。药物再利用提供了一个机会，可以通过研究已批准用于其他适应症的药物在 AD 相关方面的效果来加速这一过程。这些药物具有已知的安全性概况、药代动力学特征、制剂、剂量和制造工艺。
我们评估了截至 2020 年 2 月 27 日在 ClinicalTrials.gov 上注册的当前 AD 管道中处于 I 期、II 期和 III 期的重新定位的 AD 治疗方法。
我们确定了 53 项涉及 58 种 FDA 批准药物的临床试验。试验中 78%的药物具有潜在的疾病修饰作用机制。在管道中重新定位的药物中，20%是血液肿瘤药物，18%是源自心血管适应症的药物，14%是具有精神科用途的药物，12%是用于治疗糖尿病的药物，10%是神经科药物，其余 26%的药物则属于其他情况。这些项目中使用的知识产权策略包括使用相同的药物，但改变剂量、给药途径或制剂。大多数重新定位的试验由学术医疗中心支持，而不是由生物制药行业资助。我们将结果与欧洲试验登记处进行了比较，发现与从 ClinicalTrials.gov 得出的结果相似。
药物再利用是 AD 药物开发的常用方法，占当前 AD 管道中试验的 39%。来自许多疾病领域的治疗方法提供了在 AD 中可能有用的药物。大多数重新定位的药物都是通用药物，并且已经采用了各种知识产权策略来提高其经济价值。
