FDA Approves Xeris Biopharma’s Recorlev for Endogenous Cushing’s Syndrome in Adults

The U.S. Food and Drug Administration approved Xeris Biopharma’s Recorlev (levoketoconazole) for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.

Photo: Paul Edick, chairman and CEO of Xeris Biopharma

Endogenous Cushing’s syndrome is a rare, serious, and potentially fatal endocrine disease caused by chronic elevated cortisol exposure–often the result of a benign tumor of the pituitary gland. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period of time, which often results in characteristic physical signs and symptoms that are distressing to patients. The disease is most common among adults between the ages of 30–50, and it affects women three times more often than men. Women with Cushing’s syndrome may experience a variety of health issues including menstrual problems, difficulty becoming pregnant, and excess male hormones, primarily testosterone, which can cause hirsutism (growth of coarse body hair in a male pattern), oily skin, and acne. Multisystem complications of the disease are potentially life threatening, including metabolic changes such as high blood sugar or diabetes, high blood pressure, high cholesterol, fragility of various tissues including blood vessels, skin, muscle, and bone, and psychological disturbances such as depression, anxiety, and insomnia. Untreated, the five-year survival rate is only approximately 50 percent.

The approval of Recorlev was based upon safety and efficacy data from two positive phase 3 studies that evaluated a combined study population of 166 patients, which was representative of the adult drug-treated U.S. population with Cushing’s syndrome. The SONICS study met its primary and key secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase. LOGICS, a double-blind, placebo-controlled randomized-withdrawal study that met its primary and key secondary endpoints, confirmed the efficacy and safety of Recorlev in normalizing and maintaining therapeutic response compared with placebo.

“Cushing’s 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,” said Leslie Edwin, president of the Cushing’s Support & Research Foundation. “Today 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.”

Xeris acquired Recorlev (levoketoconazole) with its buyout of rare disease biotech Strongbridge Biopharma in October 2021. Recorlev received orphan drug designation from the FDA and the European Medicines Agency for the treatment of endogenous Cushing’s syndrome.

“With this approval, Xeris’ experienced endocrinology-focused commercial organization can begin rapidly working to help address the needs of Cushing’s syndrome patients in the U.S. who are treated with prescription therapy,” said Paul Edick, chairman and CEO of Xeris Biopharma. “Today’s announcement also reinforces the value that we saw in acquiring Strongbridge Biopharma’s attractive rare disease portfolio, which we believe will deliver compelling long-term value to our shareholders. We look forward to making Recorlev commercially available in the first quarter.”

Recorlev carries a boxed warning to watch out for hepatoxicity and QT prolongation. Most common adverse reactions (incidence > 20 percent) are 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.

Author: Rare Daily Staff