Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review

Antifungal drug development is essential as invasive fungal disease is still associated with a very high mortality rate and the emergence of resistant species in the last decade. In Europe, the European Medical Agency (EMA) approves antifungals and publishes the European Public Assessment Report (EPAR) including the information leading up to the authorisation. We looked at EMA-approved antifungals and their reports within the last 23 years. We focused primarily on the role of pharmacokinetic/pharmacodynamic indices in antifungal development and the level of information depicted in their corresponding report. Furthermore, we investigated guidelines applicable to the development process at the time and compared the content with a focus on pharmacokinetic/pharmacodynamic studies and preclinical requirements. Since 2000, six new antifungal substances have been authorised. Most were authorised for treatment of Candida infections or Aspergillus infections but also included rarer pathogens. Pharmacokinetic/pharmacodynamic indices were scarcely investigated and/or mentioned in the report. Current antifungal EMA guidelines started emphasising investigating pharmacokinetic/pharmacodynamic indices in 2010 and then again in 2016. It remains to be seen how this translates into the authorisation process for new antifungals.

Automated summary

Antifungal drug development is crucial to tackle the high mortality rate and emergence of resistant species associated with invasive fungal disease. This study examined EMA-approved antifungals and their reports over the past 23 years, focusing on the role of pharmacokinetic/pharmacodynamic indices in drug development and the information provided in the reports. The findings showed limited investigation and mention of these indices in the reports. The current EMA guidelines started emphasizing the investigation of pharmacokinetic/pharmacodynamic indices in 2010 and 2016, but its impact on the authorization process for new antifungals remains to be seen.