Strongbridge Biopharma presents new data from in vitro study of levoketoconazole
Strongbridge Biopharma announced that results from an in vitro study of levoketoconazole, the active ingredient in RECORLEV, were presented at ENDO 2018, the Annual Meeting of the Endocrine Society, taking place in Chicago, Illinois from March 17 - 20, 2018. The study aimed to characterize the potency and mechanism of 2S,4R-ketoconazole - levoketoconazole, the active ingredient of RECORLEV - inhibition of human steroidogenic enzymes in intact cells in vitro. Levoketoconazole was significantly more potent than the 2R,4S-isomer and approximately twice as potent as racemic ketoconazole for CYPs 11A1, 11B1 and 17A1; the potency differences were less marked for CYP 11B2. Ketoconazole or its enantiomers did not inhibit CYPs 19A1 or 21A2 at up to 1000 nanomolar concentration. The degree of potency differences suggests that levoketoconazole accounts for essentially all of the activity of racemic ketoconazole to inhibit cortisol biosynthesis in humans. Spectral binding constants were about three to five times higher than the IC50 for CYPs 17A1 and 11B1 in intact cells, suggesting that, for these enzymes, a second mode of inhibition not involving the canonical binding pockets of these steroidogenic enzymes accounts for a significant portion of the much greater inhibition potency of levoketoconazole as compared with its mirror-opposite isomer 2R,4S-ketoconazole. RECORLEV, or levoketoconazole, is an investigational cortisol synthesis inhibitor being evaluated in LOGICS and SONICS, two Phase 3 clinical trials for endogenous Cushing's syndrome. The safety and efficacy of RECORLEV for the treatment of endogenous Cushing's syndrome have not been established.