FDA Approves Recorlev for Adults With Endogenous Cushing’s

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by Steve Bryson PhD |

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The U.S. Food and Drug Administration (FDA) has approved Recorlev (levoketoconazole) to treat adults with endogenous Cushing’s syndrome for whom surgery is not an option or has not been effective.

The therapy is expected to be available in the U.S. in the coming months.

To ensure access to Recorlev, the company has created Xeris CareConnection, a program for patients and their caregivers, including one-on-one support, educational resources, and financial assistance. The program will also provide help with access and reimbursement to healthcare professionals.

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“We are thrilled with the FDA’s approval of Recorlev as a safe and effective treatment option for patients with endogenous Cushing’s syndrome,” Paul R. Edick, chairman and CEO of Xeris Biopharma, the company that markets the therapy, said in a press release. “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.”

The FDA decision comes on the heels of Xeris Pharmaceuticals’ recent acquisition of Strongbridge Biopharma, forming a new entity called Xeris Biopharma Holdings. The agreement encompassed Strongbridge’s pipeline, which included Recorlev.

Recorlev works by blocking the production of the stress-response hormone cortisol, which is found at abnormally high levels in Cushing’s patients, primarily due to a tumor in the brain’s pituitary gland — a form of the condition known as Cushing’s disease. The first treatment choice is surgically removing pituitary tumors, but for some patients, surgery is not an option or is ineffective at reducing cortisol levels.

In Cushing’s, besides excess cortisol, symptoms do not always occur at the same time, making diagnosis difficult. The most common signs include weight gain, increased body fat, and skin problems. As the disease progresses, other complications arise, such as high blood pressure and cholesterol, diabetes, and psychological issues like depression and anxiety.

“Cushing’s syndrome is a rare disease that can be physically and emotionally devastating to the patient,” said Leslie Edwin, president of the Cushing’s Support & Research Foundation. “Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options.”

Recorlev’s approval was based on positive findings from two Phase 3 clinical trials — SONICS (NCT01838551) and LOGICS (NCT03277690) — jointly involving a total of 166 patients.

In SONICS, nearly a third of the 94 people with endogenous Cushing’s who received Recorlev for six months saw their urine cortisol levels drop to within the normal range, without additional dose increments. LOGICS confirmed the therapy’s impact by demonstrating that treatment withdrawal caused cortisol levels to rise.

Clinical trial data also showed Recorlev reduced the risk of heart disease, lowered cholesterol and body fat, and helped control diabetes. Treatment also lessened symptoms, eased depression, and improved quality of life.

“Levoketoconazole (Recorlev) is an important and welcome new therapeutic option for clinicians to help manage patients with endogenous Cushing’s syndrome, a severe, potentially life-threatening rare disease, if not appropriately treated, with multisystem signs and symptoms,” said Maria Fleseriu, MD, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health Sciences University. “In prospective clinical studies, treatment with levoketoconazole was shown to be effective for reducing and normalizing cortisol.”

The approval was also supported by safety data from the ongoing open-label OPTICS study (NCT03621280), which will continue to monitor cortisol levels and adverse effects in patients receiving Recorlev for up to three years.

The medicine received orphan drug designation in the U.S. and Europe to treat endogenous Cushing’s syndrome, which is given to medications with the potential to treat rare medical conditions.

“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,” Edwin said. “We are grateful that the researchers worked so diligently for so long to establish the safety and efficacy of this drug.

“Rare disease patients know the importance of sharing their complicated experiences as ‘expert witnesses’, and we thank Xeris for being an early adherent to this concept,” Edwin added. “We especially want to thank the clinical trial patients who made this progress possible.”