Recorlev Also Helps to Treat Diabetes in Cushing’s Syndrome, Trial Data Show

Recorlev (levoketoconazole), Strongbridge Biopharma’s oral investigational therapy for endogenous Cushing’s syndrome, led to sustained improvements in cortisol and in blood sugar control among patients with both Cushing’s and diabetes, a subgroup analysis of Phase 3 SONICS trial data showed.

“Diabetes mellitus [type 1 diabetes] is among the more common complications related to excess levels of cortisol in people with Cushing’s syndrome,” Fredric Cohen, MD, Strongbridge’s chief medical officer, said in a press release.

“The SONICS study results provide important evidence that help further characterize the potential clinical benefit and role of Recorlev as an important treatment option for patients with Cushing’s syndrome,” Cohen added.

Findings from this analysis were reported in the study, “Levoketoconazole in the Treatment of Patients with Cushing’s Syndrome and Diabetes Mellitus: Phase 3 SONICS Results,” published in the journal Frontiers in Endocrinology.

Cushing’s syndrome is caused by a chronic overproduction of cortisol and is linked to many co-occurring illness, one of which is diabetes, characterized by poor blood sugar control.

In turn, chronically high cortisol levels are known to raise blood sugar levels. Managing diabetes in the context of Cushing’s syndrome requires a tight control over both blood sugar and cortisol.

Recorlev lowers cortisol by blocking an enzyme needed for the final step of its production in the adrenal glands, which sit stop the kidneys.

The open-label SONICS study (NCT01838551) assessed Recorlev’s ability to normalize participants’ mean 24-hour urinary free cortisol (mUFC) levels over a period of six months of maintenance therapy, without any dose increase in that period.

The study comprised a dose-titration phase and a six-month maintenance phase, followed by a six-month extended evaluation to better understsand the experimental therapy’s safety, efficacy, and tolerability.

Trial results, announced in 2018 for the main study and in 2019 its extension, showed Recorlev was well-tolerated, able to normalize urine cortisol levels, and to lower the risk of heart disease, one of the trial’s key secondary goals.

A more recent analysis of study findings, released last year, also showed Recorlev was able to ease symptoms of Cushing’s syndrome and depression, while improving patients’ quality of life, especially among female patients.

The new subgroup analysis findings focused on the effects of Recorlev in patients with Cushing’s and diabetes.

Of the 94 people with endogenous Cushing’s enrolled in SONICS, 36 (38.3%) had diabetes. Among them, 28 (77.8%) moved into the trial’s maintenance phase, along with 49 (84.5%) non-diabetic patients.

Of the 21 people with diabetes and 40 without who completed this phase, 13 (62%) diabetic and 16 (40%) non-diabetic patients achieved normal mUFC values.

Other markers of blood sugar control and heart health also improved over the course of the study, generally moreso in diabetic than non-diabetic participants. Investigators were able to rule out the effects of changes in diabetic medications, which remained stable throughout treatment.

By the end of the maintenance phase, hemoglobin A1c levels — the proportion of hemoglobin that is bound to glucose, or blood sugar — had declined from 6.9% to 6.2% in diabetic patients, and from 5.5% to 5.3% among those without diabetes.

Mean fasting blood glucose levels also dropped from 123.4 mg/dL to 104.9 mg/dL in diabetic participants, and from 92.1 mg/dL to 84.0 mg/dL in those without diabetes.

Across all of these measures, instances of worsening were rare, the investigators noted. Other key measures of cardiac health also improved in small, but still significant, ways.

Low-density lipoprotein cholesterol (commonly referred to as “bad” cholesterol), weight, and body-mass index all declined to similar degrees among those with and without diabetes.

Adverse side effects occurred at approximately the same rate between the two groups (97.2% of patients with diabetes and 98.3% of non-diabetics), with nausea and headache being the most common overall. Side effects that appeared more often among diabetics included nausea (58.3%), vomiting (19.4%), and urinary tract infection (16.7%), none of which prompted withdrawals from the study.

One non-diabetic patient withdrew due to headache. According to the company, none of the side effects appeared to be dose-related and rarely affected treatment.

Despite being “considered exploratory” and still requiring “validation from an independent study,” this subgroup analysis showed that “treatment with [Recorlev] led to sustained normalization of mUFC and improvement in glycemic control that was more pronounced in patients with [diabetes],” the researchers wrote.