Introduction: The process of drug approval involves extensive and expensive preclinical and clinical examination. Most drugs entering late-stage clinical trials get terminated for a variety of reasons including inability to achieve the primary endpoints or intolerable adverse effects. Only one-tenth of the drugs that enter clinical trials progress to Food and Drug Administration (FDA) regulatory submission.
Areas covered: This review offers insight into some of the attributes that may be responsible for a drug's failure in late-stage trials. Information from multiple open sources including PubMed articles published between 1989 and 2019, recent articles from authentic websites like www.ClinicalTrials.gov, www.fda.gov, and pharmaceutical news articles for the years between 2017 and 2021 were accumulated and summarized. Further, a few drug candidates that reached the phase III clinical trials but were discontinued at later stages have been presented as case studies.
Expert opinion: Ineluctable failures were observed due to insufficient knowledge about the mechanism of action where the disease progression stages are unclear. Other reasons were choice of patient population, late-stage treatment, and dosage. Adhering to the guidelines and recommendations provided by the regulatory authorities and learning from past failures, considerably reduce failure rates.
Keywords: Breakthrough therapy designation; clinical study design; dosage regime; late-stage clinical trial failures; patient pool; pharmaceuticals; predictive models.