Analysis of Current Industry Practices for Informing Dosing Recommendation for Patients With Renal Impairment.

Recent updates in clinical guidelines and health authority guidance documents have aimed to standardize best practices for assessing renal function; however, it remains unclear whether the pharmaceutical industry has fully adopted these recommendations. This analysis aims to describe the current methodologies used to evaluate the impact of renal impairment (RI) on drug exposure and to inform dosing recommendations for patients with RI, providing insight into current industry practices and identifying potential areas for improvement. A list of new molecular entities (NMEs) approved by the US Food and Drug Administration between 2018 and 2024 was compiled, and the clinical development strategies for assessing the impact of RI on the pharmacokinetics and safety of these NMEs were reviewed. We reviewed 192 NMEs. In dedicated renal impairment studies, renal function was assessed by the estimated glomerular filtration rate (eGFR) in 60 studies, measured GFR in 1 study, and creatinine clearance in 31 studies. We also found that 6 NMEs-5 out of 162 NMEs with non-substantial renal excretion (RE) and 1 out of 30 NMEs with substantial RE required an actionable dosing recommendation for patients with mild RI. In contrast, for severe RI, we found that 47 NMEs-30 out of 162 NMEs with non-substantial RE and 17 out of 30 NMEs with substantial RE required an actionable dosing recommendation. The findings suggest that excluding mild RI patients from phase 2 and 3 studies is not required and highlight that industry must continue efforts to harmonize drug development with clinical guidelines.