LCI699 is a novel inhibitor of 11β-hydroxylase (the final enzyme in the cortisol synthesis pathway) under development for several indications, including CD. In a recent proof-of-concept study in patients with CD (UFC >1.5× ULN), all participants (N = 12) achieved either UFC normalization or ≥50 % reduction from baseline after 70 days of treatment. While all patients experienced ≥1 AE, most were mild or moderate. Some AEs consistent with AI were reported, and resolved after dose reduction. Four patients experienced hypokalemia; all cases were managed without dose reduction, and 3 patients received oral potassium supplementation [83]. A larger-scale, 22-week expansion trial is currently underway [84]. A summary of potential therapeutic targets in CD is shown in Fig. 4 [85].
Fig. 4 Potential targets and medical therapies in Cushing’s disease. From Fleseriu, M (2012) Neurosurg Clin N Am volume 23, page 657 [85]. Reproduced with permission