Recorlev Continues to Show Meaningful Improvements, Phase 3 Trial Shows

Strongbridge Biopharma‘s Recorlev (levoketoconazole) continues to show clinically meaningful improvements in the control of cortisol among patients with endogenous Cushing’s syndrome, a Phase 3 clinical trial shows.

Cushing’s syndrome is 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 gain weight and accumulate fat around the torso (central obesity), which increases the risk of heart disease and other complications.

The Phase 3 trial (NCT01838551), known as SONICS, was launched by the company to evaluate the safety and efficacy of Recorlev for the treatment of patients with endogenous Cushing’s syndrome.

Its primary goal was to reduce cortisol levels in patients’ urine after six months of maintenance therapy with Recorlev. Secondary endpoints included decreasing the risk of heart disease, which is high among patients with Cushing’s.

SONICS top-line results announced in August 2018 showed the trial had already reached its primary and secondary endpoints, and an extended evaluation showed that Recorlev continues to be well-tolerated and induce clinically meaningful improvements in the long-term.

Now the company announced new findings from two additional analyses — one from a subgroup of patients participating in the trial who also had diabetes, and another from some of the trial’s secondary endpoints — that continue to show clinically meaningful benefits associated with Recorlev treatment in patients with Cushing’s.

The findings from the subgroup analysis of patients with diabetes were presented at the Annual Meeting of the Endocrine Society (ENDO) March 23-26 in New Orleans, Louisiana.

Of the 94 patients initially enrolled in the trial, 36 had been diagnosed with type 2 diabetes and 58 did not had any form of diabetes. Results showed that Recorlev maintenance treatment normalized the levels of cortisol in the urine of patients with and without diabetes.

Moreover, the risk of heart disease — reflected by high levels of LDL cholesterol, large waist circumference, excessive body weight, and body mass index (BMI) — was also reduced after treatment with Recorlev in all patients with and without diabetes. Patients who had diabetes experienced the greatest improvements in fasting glucose and hemoglobin A1C levels.

The rate of treatment-emergent adverse events (TEAEs) was low in all patients. The most common TEAEs experienced by patients with diabetes included nausea (58%), vomiting (19%), and urinary tract infections (17%).

“The SONICS study continues to generate important findings that help characterize the potential clinical benefit and role of levoketoconazole in the treatment of patients with endogenous Cushing’s syndrome,” Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Oregon Health Sciences University Northwest Pituitary Center, who presented the data, said in a press release.

“The subgroup analysis of Cushing’s syndrome patients with diabetes mellitus — among the more common comorbidities associated with the disease — not only shows similar levels of cortisol control compared to patients without, but also more pronounced improvements in key glycemia measures, such as hemoglobin A1c and fasting blood glucose, and other cardiovascular risk markers, such as LDL cholesterol. In both treatment groups, the overall safety profile was acceptable,” Fleseriu said.

The findings from the additional analyses of the trial’s secondary endpoints were presented at the 16th Annual International Pituitary Congress (IPC) March 20-22 in New Orleans, Louisiana.

Results showed that six months of maintenance treatment with Recorlev successfully decreased levels of cortisol in the patients’ urine and saliva. However, the reduction of cortisol in saliva was less frequent than in urine, suggesting an overall, but still partial, normalization of cortisol levels.

Findings also confirmed that Recorlev was generally well-tolerated by patients and did not trigger any sudden adverse events over the course of the study.