Prodrugs – Recent approvals and a glimpse of the pipeline

Prodrugs offer a versatile strategy to overcome flaws of viable drug candidates or clinically approved drugs. However, the strategic importance of prodrugs in the pharmaceutical industry has often been challenged, and prodrugs are often considered as the last option after lead optimization and when the selected drug candidate has faced significant pharmaceutical and pharmacokinetic limitations. Based on recent success in marketed drugs, prodrug strategy should clearly be considered already in early stages of lead optimization. During the past five years or so, prodrugs have accounted for about 10% of all small molecular weight drugs that have come to the market. In 2015 alone, the FDA approved seven prodrugs, which gives a prodrug prevalence of over 20% among the small molecules or over 15% among the total amount of the FDA approved drugs that year. A great number of various prodrugs are also undergoing late stage clinical trials. The pharmaceutical industry will therefore continue to depend on prodrugs for the foreseeable future. In this review, we will present the state of the art in the design of the prodrugs launched by the FDA since 2015. We will also provide an overview of some interesting late stage clinical prodrug candidates. We hope this review will demonstrate potential of prodrug strategies and facilitates the use of prodrugs in drug discovery projects.