Drug repurposing: a systematic review on root causes, barriers and facilitators

Abstract

Background Repurposing is a drug development strategy receiving heightened attention after the Food and Drug Administration granted emergency use authorization of several repurposed drugs to treat Covid-19. There remain knowledge gaps on the root causes, facilitators and barriers for repurposing. Method This systematic 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 (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 top reasons. Key barriers to repurposing include inadequate resources (n = 42), trial data access and transparency around abandoned compounds (n = 20) and expertise (n = 11). Additional barriers include uncertainty about the value of repurposing (n = 13), liability risks (n = 5) and intellectual property (IP) challenges (n = 26). Facilitators include the ability to form multi-partner collaborations (n = 38), access to compound databases and database screening tools (n = 32), regulatory modifications (n = 5) and tax incentives (n = 2). Conclusion Promising drugs are commonly shelved due to insufficient efficacy or superiority to alternate therapies, poor market prospects, and industry consolidation. Inadequate resources and data access and challenges negotiating IP are key barriers to repurposing reaching its full potential as a core approach in drug development. Multi-partner collaborations and the availability 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. Trial registration The protocol was registered on Open Science Framework (https://osf.io/f634k/) as it was not eligible for registration on PROSPERO as the review did not focus on a health-related outcome.

Alzheimer's disease drug development pipeline: 2023

“…Eighty percent of repurposed agents are funded through these mechanisms. The disproportionately smaller role played by the biopharmaceutical industry compared to NIH, academics, advocacy, and philanthropic entities in the development of repurposed agents reflects the difficulty ofprotecting intellectual property for generic drugs that comprise the foundation for marketability and return on investment 10,11. Deployment and marketing of a successfully developed repurposed compound requires substantial funding.…”

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inPlasmodium vivaxHypnozoites

“…This report also adds to the broader discussion surrounding the successes and challenges of drug repurposing ( 28 ). Of the hits we identified, colforsin daropate, rhodamine 123, and poziotinib are used for cancer indications and, like the hydrazinophthalazines, have known human targets, implying that selectivity and off-target toxicity are hurdles to be addressed if repurposing for radical cure is to be successful.…”

“…Regardless, these results highlight that in vivo P. vivax relapse models should be further developed and validated, as those hits lacking activity in P. cynomolgi might be abandoned for no other reason than the inability to demonstrate in vivo efficacy prior to first-inhuman studies (27). This report also adds to the broader discussion surrounding the successes and challenges of drug repurposing (28). Of the hits we identified, colforsin daropate, rhodamine 123, and poziotinib are used for cancer indications and, like the hydrazinophthalazines, have known human targets, implying that selectivity and off-target toxicity are hurdles to be addressed if repurposing for radical cure is to be successful.…”

Harnessing Monocytes for a Liposomal Rosiglitazone-Mediated Anti-Inflammatory Effect

“…Our work's premise is to utilize a drug's known polypharmacology properties to unlock novel therapeutic opportunities by redesigning its drug delivery system (28). Rosiglitazone is a proven, highly effective drug in treating type Ⅱ diabetes mellitus.…”