FDA Approves Levoketoconazole for Cushing Syndrome

Miriam E. Tucker

January 04, 2022

The US Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.

Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.

Levoketoconazole inhibits cortisol synthesis. The FDA approval was based on efficacy and safety data from two phase 3 studies involving a total of 166 patients with endogenous Cushing syndrome. In both the open-label, single-arm SONICS study and the randomized, placebo-controlled LOGICS trial, the drug significantly reduced and normalized mean urinary free cortisol levels and improved several secondary endpoints. The ongoing open-label OPTICS study will gather long-term data.

The Recorlev label includes boxed warnings about the potential for life-threatening hepatotoxicity and QT prolongation. Prior to and during treatment, patients should undergo liver enzyme testing, ECG, and correction of hypokalemia and hypomagnesemia.  

The most common adverse reactions (occurring in > 20%) include 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.

"Cushing syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options...We are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing's community," Leslie Edwin, president of the Cushing's Support & Research Foundation, said in a Xeris statement.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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