The Food and Drug Administration (FDA) has approved Recorlev® (levoketoconazole) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not an option or has not been curative.
Recorlev is a cortisol synthesis inhibitor. The approval was based on data from the phase 3 SONICS (ClinicalTrials.gov Identifier: NCT01838551) and LOGICS (ClinicalTrials.gov Identifier: NCT03277690) studies that evaluated the efficacy and safety of Recorlev in patients with endogenous Cushing syndrome.
The open-label SONICS trial included patients who received an initial dose of Recorlev 150mg twice daily and were titrated in 150mg increments to a therapeutic dose. The LOGICS trial compared the effect of withdrawing Recorlev treatment for placebo vs continuing treatment with Recorlev on cortisol therapeutic response in patients for up to 8 weeks.
Findings from the SONICS trial showed that 30.9% (n=29/94) of patients achieved normalization of mean urinary free cortisol (UFC) after 6 months of maintenance treatment with Recorlev, without a dose increase (P <.025). Treatment with Recorlev 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).
Findings from the LOGICS trial showed that among the 39 patients who had normal mUFC at baseline, 52.4% (n=11/21) of the Recorlev group and 5.6% (n=1/18) of the placebo group had normal mUFC at the end of the randomized withdrawal phase (treatment difference: 46.8% (95% CI, 16.5-70.2).
The most common adverse reactions (incidence >20%) reported with Recorlev were nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema. Recorlev carries a Boxed Warning regarding the risks for hepatotoxicity and dose-related QT interval prolongation.
Recorlev is supplied as 150mg tablets of levoketoconazole in 50-count bottles and is expected to be available in the first quarter of 2022.
- Xeris Biopharma Announces U.S. FDA Approval of Recorlev® (levoketoconazole) for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome. News release. Xeris Biopharma. December 30, 2021. Accessed January 3, 2022. https://www.businesswire.com/news/home/20211230005308/en/Xeris-Biopharma-Announces-U.S.-FDA-Approval-of-Recorlev%C2%AE-levoketoconazole-for-the-Treatment-of-Endogenous-Hypercortisolemia-in-Adult-Patients-With-Cushing%E2%80%99s-Syndrome
- Recorlev. Package insert. Xeris Biopharma; 2021. Accessed January 3, 2022. https://www.recorlev.com/full-prescribing-information.pdf