Recorlev Up for FDA Approval as Endogenous Cushing’s Syndrome Treatment

Strongbridge Biopharma has filed an application with the U.S. Food and Drug Administration (FDA) seeking the approval of Recorlev (levoketoconazole) to treat people with endogenous Cushing’s syndrome, the company announced.

The application is supported by results from two Phase 3 studies, SONICS (NCT01838551) and LOGICS (NCT03277690), which showed that Recorlev lead to sustained normalization of cortisol levels in treated patients.

Safety data from the ongoing OPTICS study (NCT03621280) was included in the NDA. In this open-label extension trial, patients from previous studies will continue being treated with Recorlev for up to three years.

“The submission of the New Drug Application for Recorlev (levoketoconazole) represents not only a significant milestone for Strongbridge but also for the Cushing’s syndrome community as a whole,” said John H. Johnson, chief executive officer of Strongbridge Biopharma.

An FDA review is likely to take 10 months. If approved, Strongbridge expects to launch Recorlev in the U.S. in early 2022.

Endogenous Cushing’s syndrome is characterized by the excessive production of cortisol, usually due to a benign tumor in the pituitary (Cushing’s disease) or adrenal glands. Abnormally high cortisol levels leads to weight gain and fat accumulating around the torso (central obesity), which increases the risk of heart disease and other medical complications.

According to Strongbridge, currently nearly 40% of patients with endogenous Cushing’s syndrome are unable to control their cortisol levels with prescribed therapies, highlighting the need for more effective medicines.

“As an organization focused on developing treatments for underserved rare disease patient populations, we are one step closer to helping address the needs of the estimated 8,000 Cushing’s syndrome patients in the U.S. who are treated with prescription therapy, many of whom, as we learned in our market research, are not well-controlled with current therapies,” said Johnson.

Recorlev is a next-generation oral cortisol synthesis inhibitor, meaning it is designed to keep the adrenal glands from producing too much cortisol. It has been given orphan drug status by the FDA and European Medicines Agency (EMA) as a potential treatment of endogenous Cushing’s syndrome.

The Phase 3 SONICS trial was a non-randomized study evaluating the safety and efficacy of Recorlev in 94 adults with a confirmed diagnosis of Cushing’s syndrome.

Following a first a dose-escalation phase to determine the appropriate Recorlev dose, a maintenance phase administered the therapy at that dose (600 mg twice per day) for six months. This was followed by an extension phase, in which patients received Recorlev for an additional six months, with the possibility of dose adjustments.

Top-line results showed that the trial successfully achieved its primary goal, with 30% of patients showing normalized cortisol levels after six months of Recorlev, without any dose increase during that period. Secondary goals were also achieved, including lowering heart disease risk. Additional analysis found that Recorlev lessened disease symptoms and depression, and improved patient’s quality of life.

The LOGICS trial continued to evaluate Recorlev’s effectiveness and safety in patients with endogenous Cushing’s syndrome. The study enrolled people new to the investigative treatment, as well as those given the medication in SONICS.

LOGICS’ main goal was to assess the effects of Recorlev withdrawal on the levels of cortisol in the patients’ urine, compared with patients who remained on Recorlev.

In an initial withdrawal phase, patients were assigned randomly to either Recorlev (up to a dose of 1,200 mg) or to a placebo for about eight weeks. This was followed by a restoration phase, during which all patients received Recorlev.

Top-line data showed that by the end of the randomized-withdrawal phase, the proportion of patients with rising urine cortisol levels was 54.5% higher among those on a placebo than among those treated with Recorlev (95.5% vs. 40.9%). These patients saw their cortisol starting to drop after a median of 22 days of rescue treatment.

The percentage of patients whose urine cortisol levels were within normal range by the end of the withdrawal phase was 45.5% higher among those treated with Recorlev, compared with those given a placebo.

“We want to thank the patients, their families, investigators, collaborators, and employees who have contributed to the Recorlev clinical program leading to this important regulatory milestone,” said Fredric Cohen, MD, chief medical officer for Strongbridge.