Pivonello R, Fleseriu M, Newell-Price J, et al. - The outcomes from the pivotal phase 3 study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11β-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing disease were reported in this work. In LINC 3, a prospective, multicentre, open-label, phase 3 study, there was a double-blind randomized withdrawal period comprising of four periods. From 66 hospital sites and private clinical practices in 19 countries, recruitment of patients aged 18–75 years, with confirmed persistent or recurrent Cushing disease was done. In period 1, all participants received open-label osilodrostat; it was adjusted every 2 weeks (1–30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h urinary free cortisol [UFC] concentration and safety until week 12. In period 2, weeks 13–24, osilodrostat was administered at the therapeutic dose assessed during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomized (1:1) to either continue osilodrostat or switch to placebo for 8 weeks. Ineligible participants continued to receive open-label osilodrostat. In period 4, weeks 35–48, open-label osilodrostat was provided to all participants until core-study end. Findings revealed rapid reduction in mean 24-h UFC in correlation with receiving twice-daily osilodrostat; patients sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. They support osilodrostat to be an effective new therapeutic option that is approved in Europe for the management of endogenous Cushing syndrome and in the USA for Cushing disease.