Effective treatments for both existing and emerging diseases may already be available on pharmacy shelves. Many approved drugs have more than one use or benefit but are rarely researched beyond the initial indication for which they are approved. Such research to identify new indications for already-approved drugs is known as drug repurposing.
Drug repurposing is viewed by some as a faster, cheaper, and less risky approach to drug development. The development of a de novo drug is reported to take an average of 8-10 years and cost as much as $2.8 billion. Since they have been approved by a regulatory body, repurposed compounds have already demonstrated safety in humans. Therefore, earlier stages of drug discovery and clinical trials can be bypassed, and development efforts can focus on demonstrating efficacy for the new indication. Because of these advantages, there has been growing interest in drug repurposing in recent years, particularly in disease areas with poor commercial markets. Drug repurposing of approved drugs gained further attention and played an important role in response to the COVID-19 pandemic, as was underscored by Greenblatt et al.’s recent Health Affairs article.
Despite the advantages and potential of drug repurposing, several challenges and barriers exist. In a recent systematic review, Miller et al. found six common barriers to repurposing drugs: inadequate resources, trial data access and transparency around abandoned compounds, expertise, uncertainty about value, liability risks, and intellectual property challenges. Consistent with these conclusions, Greenblatt et al. also found “weak incentives and organizational barriers,” gaps in regulatory supports, a lack of clarity on the risk-benefit trade-off of drug repurposing trials, and poor coordination in the context of repurposing for COVID-19.
Addressing these identifiable challenges and barriers is essential for pandemic preparedness efforts. On Day 1 of an emerging pandemic or health threat, drug repurposing represents a critical path to quickly identify potential treatments along with de novo drug development and repositioning of compounds in development which have not received regulatory approval. In the case of COVID-19, most United States’ (US) clinical trials in the first two quarters of 2020 included at least one repurposed Food and Drug Administration (FDA) approved drug. Although, as time passed the majority of trials were focused on new drugs. This exemplifies that drug repurposing stands as the first line of defense against a new threat and serves as an essential complement to de novo drug development efforts.
A central and elusive question among experts is how to define success in drug repurposing efforts. On one hand, using traditional metrics of an individual company’s internal rate of return (IRR), repurposing efforts have been viewed as largely unsuccessful relative to financial investment and number of regulatory approvals. However, an alternative view is that this metric is too narrow, and measures of success need to include the number of lives saved, patients who avoid hospitalization, and speed of adoption compared to de novo research and development. In their Health Affairs article, Greenblatt et al. argued that the inclusion of repurposed drugs in treatment guidelines (National Institutes of Health (NIH) and Infectious Disease Society of America) for COVID-19 demonstrates that drug repurposing “lived up to its promise of quickly leading to the development of effective COVID-19 therapeutics.” By this standard, drug repurposing for COVID-19 was a success.
Although definitions of what represents success in drug repurposing efforts vary, the White House has demonstrated an understanding of the value of expediting drug development in response to public health threats. In October 2022, it released its “Strategy to Strengthen Health Security and Prepare for Biothreats.” The strategy includes ambitious targets for therapeutic development in response to an emerging pandemic, including the identification, testing, authorization, manufacture, and deployment of repurposed therapeutics within 90 days of determination of a potential nationally or internationally significant biological incident. Along with investments to ensure that we have strong clinical trial infrastructure and a ready base for manufacturing, maintaining an efficient and effective system for drug repurposing is a critical strategy to achieve these goals.
To that end, the Duke-Margolis Center for Health Policy convened a private roundtable meeting on drug repurposing for pandemic innovations on January 23, 2023. The meeting sought to understand lessons learned on drug repurposing for recent public health threats and determine the key research questions to establish an effective and efficient ecosystem for repurposing in response to future emerging pandemics and health threats. The purpose of this white paper is to provide a comprehensive look at drug repurposing for pandemics, lessons learned, and outstanding research questions. Building on initial recommendations and ideas shared at this meeting, we aim to provide insight into the value of drug repurposing, highlight best practices, and identify important areas where more work is needed to clarify priorities and align incentives among stakeholders.