1. Consideration of the Root Causes in Candidate Attrition During Oncology Drug Development.
- Author
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Kuo, Yin‐Ming and Barrett, Jeffrey S.
- Subjects
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ANTINEOPLASTIC agents , *IMMUNE checkpoint inhibitors , *LITERATURE reviews , *ANGIOTENSIN-receptor blockers , *DRUG discovery , *BREAST , *PHARMACOGENOMICS - Abstract
This article explores the high attrition rate of oncology drugs, which leads to increased costs for drug developers. Only 1 in 20 new chemical entities in oncology receive approval from regulatory authorities. The primary reasons for drug attrition have shifted from inappropriate pharmacokinetics to a lack of efficacy and safety. Strategies to reduce attrition include careful selection of animal models and biomarkers, as well as the development of biologics. Safety and toxicology are the main sources of drug failure. The article also includes a survey of experts in the field to gather insights on attrition of oncology drugs. The article discusses the trends and factors contributing to the discontinuation of oncology drugs during drug development. The total number of failed drugs has increased over time, with a 2-fold increase in 8 years. Half of the discontinued drugs occurred in Phase 1 trials, indicating that early-stage attrition minimizes financial loss. The reasons for drug attrition varied, with efficacy and strategic considerations being the major factors. Small molecules had a higher attrition rate compared to antibodies and other drug classes. Lung cancer was the most targeted indication for discontinued drugs. The article also highlights the complexities of cancer treatment and the importance of physicochemical properties, target validation, biomarkers, and adaptive clinical trials in drug development. It emphasizes the need for improved drug development strategies, such as drug repurposing and combination treatments. The article concludes by suggesting that adaptive clinical trial designs and effective communication with regulatory agencies are [Extracted from the article]
- Published
- 2024
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