The Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for levoketoconazole (Recorlev®) for the treatment of endogenous Cushing syndrome.
Levoketoconazole, a pure 2S,4R enantiomer of ketoconazole, is an adrenal steroidogenesis inhibitor. The NDA submission is supported by data from the phase 3 SONICS (ClinicalTrials.gov: NCT01838551) and LOGICS (ClinicalTrials.gov: NCT03277690) studies that evaluated the efficacy and safety of levoketoconazole in adults with endogenous Cushing’s syndrome.
The open-label SONICS trial included 94 patients who received an initial dose of levoketoconazole 150mg twice daily and were titrated in 150mg increments to a therapeutic dose. The LOGICS trial compared the effect of withdrawing levoketoconazole treatment to placebo vs continuing treatment with levoketoconazole on cortisol therapeutic response in 44 patients for up to 8 weeks.
Findings from the SONICS trial showed that 30% of patients achieved normalization of mean urinary free cortisol (UFC) after 6 months of maintenance treatment with levoketoconazole, without a dose increase (P <.025). Treatment with levoketoconazole was also associated with statistically significant and clinically meaningful improvements from baseline in fasting blood glucose, hemoglobin A1C, total cholesterol, low density lipoprotein (LDL)-cholesterol, body weight and body mass index (P <.0001 for each).
Results from the LOGICS trial showed that 54.5% more patients who were withdrawn to placebo had a loss of mUFC response at the end of the randomized-withdrawal phase (primary endpoint) compared with those who remained on levoketoconazole (P =.0002). Levoketoconazole also met the secondary endpoint with 45.5% more patients maintaining mUFC normalization compared with placebo (P =.0015).
As for safety, the most commonly reported adverse events with levoketoconazole were nausea, hypokalemia, headache, hypertension, and diarrhea.
A Prescription Drug User Fee Act (PDUFA) target date of January 1, 2022 has been set for the application.
- Strongbridge Biopharma plc announces U.S. Food & Drug Administration (FDA) filing acceptance of New Drug Application (NDA) for Recorlev® (levoketoconazole) for the treatment of endogenous Cushing’s syndrome. [press release]. Dublin, Ireland and Trevose, PA: Strongbridge Biopharma plc; May 13, 2021.
- Strongbridge Biopharma plc presents detailed results from pivotal phase 3 LOGICS study of Recorlev® (levoketoconazole) for the treatment of endogenous Cushing’s syndrome at the 2021 Annual Meeting of the Endocrine Society (ENDO). [press release]. Dublin, Ireland and Trevose, PA: Strongbridge Biopharma plc; March 20, 2021.