Recorlev Shows Promise for Endogenous Cushing’s Syndrome, Results Show

Recorlev (levoketoconazole) safely and successfully reduces the levels of cortisol in patients with endogenous Cushing’s syndrome, according to top-line results of a Phase 3 clinical trial.

Cushing’s syndrome occurs due to abnormally high levels of cortisol, mainly caused by prolonged exposure to cortisol-like steroid medications and less commonly by excessive production of cortisol by the body, due to a tumor (endogenous Cushing’s syndrome).

The higher-than-normal production of cortisol hormone may cause weight gain, high blood pressure, and elevated levels of cholesterol and sugar in the blood, which are associated with a higher risk of cardiovascular diseases.

Recorlev is an oral suppressor of cortisol production being developed by Strongbridge Biopharma to treat endogenous Cushing’s syndrome.

A multi-center, open-label Phase 3 study, called SONICS (NCT01838551), evaluated the safety and effectiveness of Recorlev in patients with endogenous Cushing’s syndrome. Strongbridge recruited 94 patients at 42 sites in North America, Europe, and the Middle East.

The study was conducted in three parts: a dose-escalation phase to determine the appropriate Recorlev dose; a maintenance phase in which patients received the established appropriate dose for six months; and a final extended phase, in which patients received Recorlev for an additional six months, with the possibility of dose adjustments.

The study’s primary goal was a reduction in the levels of cortisol in the patients’ urine after six months of maintenance treatment, without any dose increase during that period. Among secondary goals was a reduction in the risk of cardiovascular disease, through the assessment of multiple cardiovascular risk markers.

According to Strongbridge, the SONICS study achieved its primary goal, with 30% of patients showing normalization of cortisol levels after six months of Recorlev, which was statistically significant.

Recorlev treatment also improved multiple cardiovascular risk markers, including cholesterol levels, blood sugar, body weight, and body mass index, which had clinical significance.

Recorlev was generally well-tolerated, with nausea (32%) and headache (28%) as the most common adverse side effects associated with treatment. Fourteen patients (14.9%) reported one or more serious adverse effects, but those were considered to be related to treatment in only four of them.

Twelve participants (12.8%) discontinued treatment due to adverse events, and one patient died of causes not associated with Recorlev treatment.

Only three patients (3.2%) had a significant increase of the levels of alanine aminotransferase — a liver enzyme used to assess liver damage — which was fully resolved with proper medication and not associated with further complications.

“The impressive top-line results of the SONICS study suggest that Recorlev … is an effective and well tolerated cortisol synthesis inhibitor in Cushing’s syndrome,” Fred Cohen, Strongbridge Biopharma’s chief medical officer, said in a press release.

“Based on these compelling data, we look forward to discussing the potential for accelerated approval of Recorlev with the FDA and to continuing our discussions with regulators around the world,” Cohen said.

Strongbridge is recruiting patients with endogenous Cushing’s syndrome for a randomized, placebo-controlled, Phase 3 study called LOGICS (NCT03277690), which will include participants of the SONICS study and patients who never have taken Recorlev.