Phase III SONICS study of Recorlev for Cushing's syndrome published in The Lancet Diabetes & Endocrinology.- Strongbridge Biopharma

Strongbridge Biopharma announced that comprehensive results from the positive pivotal Phase III SONICS study of Recorlev (levoketoconazole) for the potential treatment of endogenous Cushing's syndrome were published online in The Lancet Diabetes & Endocrinology. SONICS enrolled 94 patients experiencing a mean urinary free cortisol (mUFC) of 671?4 nmol/24 hours (243?3 ?g/24 hours), which is nearly five times the upper normal limit (UNL). Seventy seven patients advanced into the six-month maintenance phase, and 61 patients completed this phase of the study. The SONICS study met its primary endpoint, with 30 percent of patients achieving mUFC normalization at the end of the maintenance phase among the intent-to-treat (ITT) population (n=94), without a dose increase (p=0.015 vs null hypothesis of at least 20%). The analyses found for the patients who advanced into the maintenance phase, 81 percent had achieved mUFC normalization by the end of the dose titration phase and 36 percent of patients achieved normalization of mUFC during the maintenance phase, regardless of dose increase, ITT analysis.

In addition, 46 percent of patients achieved a 50 percent or more decrease or normalization of mUFC during the maintenance phase, regardless of dose increase, ITT analysis and 62 percent of maintenance phase completers had normalized mUFC at month six based on 55 maintenance phase completers with both baseline and month six mUFC data available. For key secondary endpoints of cardiovascular risk biomarkers, such as fasting glucose, weight and LDL-cholesterol, Recorlev demonstrated statistically significant and clinically meaningful mean improvements from baseline at the end of the maintenance phase. Recorlev was generally well-tolerated during the dose titration and maintenance phases of the study and no unexpected safety signals were observed. The most common adverse effects were nausea (32%) and headache (28%). Adverse events leading to discontinuation of treatment occurred in 12 of the 94 patients (13%) enrolled.

See: 'Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial" Maria Fleseriu et al. The Lancet Diabetes and Endocrinology September 18, 2019 DOI:https://doi.org/10.1016/S2213-8587(19)30313-4