Rare Daily Staff

Strongbridge Biopharma reported comprehensive results from the positive pivotal phase 3 SONICS study of Recorlev, for the potential treatment of endogenous Cushing’s syndrome, a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure.

The results were published online in The Lancet Diabetes & Endocrinology.

Cushing’s syndrome is an endocrine disorder leading to excess secretion of cortisol, a hormone produced by the adrenal gland. Causes can vary and include noncancerous tumors on the adrenal glands, tumors in the pituitary gland, or long-term use of corticosteroid medications. Symptoms of Cushing’s syndrome include upper body obesity, fatigue, muscle weakness, high blood pressure, backache, high blood sugar, easy bruising, and bluish-red stretch marks on the skin. It mostly affects adults between age 20 and 50 years.

Recolrev is an experimental cortisol synthesis inhibitor in development for the treatment of patients with endogenous Cushing’s syndrome. It is believed to significantly suppress serum cortisol in healthy subjects and has the potential to be a next-generation cortisol inhibitor.

The SONICS trial enrolled 94 patients experiencing a mean urinary free cortisol (mUFC) concentration nearly five times the upper normal limit. Seventy seven patients advanced into the six-month maintenance phase, and 61 patients completed this phase of the study. The SONICS study met its primary endpoint, with 30 percent of the 94 patients achieving mUFC normalization at the end of the maintenance phase without a dose increase. For the patients who advanced into the maintenance phase, 81 percent had achieved mUFC normalization by the end of the dose titration phase, and 36 percent of patients achieved normalization of mUFC during the maintenance phase, regardless of dose increase.

“The phase 3 SONICS study demonstrated Recorlev, the 2S,4R enantiomer of ketoconazole, was safe and effective in a representative population of patients with endogenous Cushing’s syndrome,” said Maria Fleseriu, professor of Medicine and Neurological Surgery and director of the Oregon Health Sciences University Northwest Pituitary Center and principal investigator of the study. “Importantly, treatment with Recorlev was shown to be effective for reducing and normalizing mean urinary free cortisol (mUFC) concentrations and biomarkers of cardiovascular risk, as well as improving clinical signs and quality of life in patients with endogenous Cushing’s syndrome. These data are highly encouraging given medical needs remain very high for this rare endocrine disorder, despite the availability of approved treatments.”

Recorlev also demonstrated statistically significant mean improvements from baseline at the end of the maintenance phase for key secondary endpoints of cardiovascular risk biomarkers, such as fasting glucose, weight and LDL-cholesterol. It was generally well-tolerated during the dose titration and maintenance phases of the study and no unexpected safety signals were observed. Adverse events leading to discontinuation of treatment occurred in 12 of the 94 patients enrolled.

Fredric Cohen, chief medical officer of Strongbridge, said he expects top-line data from LOGICS, a second phase 3 trial, at the end of the first quarter of 2020, and a submission of an application to market the drug at the end of the third quarter of 2020.

Recorlev has received orphan drug designation from the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of endogenous Cushing’s syndrome.

Photo: Fredric Cohen, chief medical officer of Strongbridge

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