Recorlev Safe, Effective Over Long Term for Treatment of Cushing’s, Phase 3 Data Suggest

Long-term treatment with Strongbridge Biopharma‘s Recorlev (levoketoconazole) continues to be well-tolerated and to induce clinically meaningful improvements in endogenous Cushing’s syndrome patients, an extended evaluation of a Phase 3 clinical trial shows.

Cushing’s syndrome is a medical condition caused by the excessive production of the hormone cortisol by the adrenal glands, which sit atop the kidneys. When cortisol levels rise to unhealthy levels — a condition known as hypercortisolism — patients start gaining weight and accumulate fat around their torso (central obesity), which increases the risk of heart disease and other medical complications.

The Phase 3 trial (NCT01838551), known as SONICS, designed to evaluate the safety and efficacy of Recorlev for the treatment of patients with endogenous Cushing’s syndrome, was divided into three different phases.

First, a dose-escalation phase was intended to determine the best dose of Recorlev to normalize cortisol levels, starting at 300 milligrams daily, increasing by 150 mg increments until the optimal dose was reached. Then, a maintenance phase treated patients with the established dose of Recorlev and monitored them for six months. Finally, an extended evaluation phase was conducted, in which patients were treated with Recorlev for an additional six months to assess the long-term safety, tolerability, and cost-effectiveness of the treatment.

The primary goal of the study was to reduce cortisol levels in the patients’ urine by the end of the six-month maintenance treatment without having to increase the doses of Recorlev. Secondary goals included decreasing the typically high risk of heart disease among Cushing’s patients.

According to SONICS’ top-line results reported last August, the trial successfully achieved its primary and secondary goals. Additional analyses from the patients who concluded the six-month maintenance treatment showed that Recorlev was able to lower patients’ cortisol levels significantly, regardless of their levels at the beginning of the study.

Of the 61 patients who completed the maintenance phase of SONICS, 60 were eligible to participate in the extended evaluation phase of the study, and 46 successfully completed it. Clinical data was collected twice at three-month intervals.

Recorlev treatment was well-tolerated during the extended evaluation phase of the study. Only four patients (6.7%) interrupted treatment due to adverse events, and none of the patients experienced liver complications. Remarkably fewer patients experienced nausea (2% vs. 32%) and headaches (7% vs. 28%) associated with treatment over the course of the extended evaluation phase, compared with the previous two phases of the study. No new drug-related safety signals were found.

Efficacy data showed that Recorlev normalized urine cortisol levels in 41% of the patients and led to a clinical improvement of at least 50% in 68% of the patients. In addition, clinically meaningful improvements were also found in heart disease risk markers (e.g., total and LDL-cholesterol, fasting glucose, hemoglobin A1C).

“We are encouraged by the top-line results from the SONICS extended evaluation phase. Recorlev (levoketoconazole) treatment was associated with no new clinically relevant liver-related findings or other new safety signals, while demonstrating long-term efficacy to reduce mean urinary free cortisol, or mUFC, as well as key cardiovascular risk markers such as weight and LDL-cholesterol,” Fredric Cohen, MD, chief medical officer of Strongbridge Biopharma, said in a press release.

“A Type C meeting with FDA is progressing as planned in the first quarter of 2019 to seek guidance on the regulatory path forward to obtain marketing approval for Recorlev for the treatment of endogenous Cushing’s syndrome, and we anticipate providing an update in the second quarter of 2019,” Cohen added.