Why promising drugs are shelved and barriers and facilitators to their re-purposing: A systematic literature review (preprint)

Background: Repurposing is a drug development strategy receiving heightened attention after the FDA granted emergency use authorization of several repurposed drugs to treat Covid-19. There remain knowledge gaps on facilitators and barriers for repurposing and why promising drug candidates get shelved in the outset. Method: This systematic literature review used controlled vocabulary and free text terms to search ABI/Informa, Academic Search Premier, Business Source Complete, Cochrane Library, EconLit, Google Scholar, Ovid Embase, Ovid Medline, Pubmed, Scopus, and Web of Science Core Collection databases for the characteristics, reasons and example of companies deprioritizing development of promising drugs and barriers, facilitators and examples of successful re-purposing. Results: We identified 11,814 articles, screened 5,976 for relevance, found 437 eligible for full text review, 115 of which were included in full analysis. Most articles (66%, 76/115) discussed why promising drugs are abandoned, with lack of efficacy, or superiority to other therapies, for the studied indication (n=59), strategic business reasons (n=35), safety problems (n=28), research design decisions (n=12), the complex nature of a studied disease or drug (n=7) and regulatory bodies requiring more information (n=2) among the top. Repurposing barriers include inadequate resources (n=42), expertise (n=11), intellectual property challenges (n=26), poor data access (n=20), uncertainty about the value of repurposing (n=13), and liability risks (n=5). Repurposing facilitators include multi-partner collaborations (n=38), access to compound databases and corresponding screening tools (n=32), regulatory modifications (n=5), and tax incentives (n=2).Conclusion: Sponsors deprioritize development of promising drugs due to insufficient efficacy or superiority to other therapies for studied indications or populations, perceived market prospects, and industry consolidation. Inadequate resources and data access and challenges negotiating IP are key barriers needing reform for repurposing to reach its full potential as a core approach in drug development. Multi-partner collaborations and the creation, accessibility, and use of compound databases and tax incentives are key facilitators for repurposing. More research is needed on the current value of repurposing in drug development and how to better facilitate resources to support it, where valuable, especially financial, staffing for out-licensing shelved products, and legal expertise to negotiate IP agreements in multi-partner collaborations.Registration: The protocol was registered on Open Science Framework (https://osf.io/f634k/) as it was not eligible for registration on PROSPERO.

Access to COVID-19 Vaccines in High-, Middle-, and Low-Income Countries Hosting Clinical Trials (preprint)

The COVID-19 pandemic has led to the rapid development of multiple vaccines, vaccines that were tested in clinical trials located in several countries around the world. Because prior research has shown that pharmaceuticals do not receive consistent and timely authorization for use in lower-income countries where they are tested, we conducted a cross-sectional study examining the authorization or approval and delivery for COVID-19 vaccines recommended by the World Health Organization (WHO) in the countries where they were tested. While countries of varying incomes have largely authorized the COVID-19 vaccines tested within their populations for use, high-income countries have received proportionately more doses, enabling them to more fully vaccinate their populations. As many lower-income countries continue to experience inequitable shortfalls in COVID-19 vaccine supply amid the ongoing pandemic, efforts must be undertaken to ensure timely access in countries across all income groups, including those hosting clinical trials.