A Systematic Assessment of Drug Repurposing Efforts Against COVID‐19: Limited Successes and Key Challenges

Objective: Drug repurposing is a promising alternative for the development of new treatment options. During the COVID‐19 pandemic, multiple repurposed drugs were tested and some became pillars of treatment and the standard of care. However, whether the benefits of drug repurposing over de novo drug development actually materialize remains an open question, especially since former analyses have been complicated by challenges to attract enough funding for late‐stage clinical trials. Methods: We conducted a systematic analysis of repurposing efforts against COVID‐19 focusing on the 100 most frequently prescribed drugs in the United States including both preclinical and clinical work. Results: In total, we identify (pre)clinical research for 42 drugs and evidence of anti‐COVID‐19 effects for 33 drugs. The rate of studies with positive results decreased from in vitro to animal studies to randomized clinical trials. While we find positive RCTs for 12 drugs, these trials had mostly low participant numbers and several reported endpoints of minor clinical relevance. Assessment of the methodological quality assessment indicates that preregistration, blinding, and power calculations are currently still an exception in preclinical studies. In the end, none of these drugs were recommended by treatment guidelines. Conclusions: Our analysis underlines the large efforts undertaken to repurpose commonly prescribed drugs against COVID‐19, which eventually proved futile. This finding may serve as a cautionary example for drug repurposing also for other fields of biomedicine. However, it should be noted that a limitation of this study is its focus on only the 100 most prescribed drugs in the United States, as we chose to analyze widely available and generally affordable medications.