Recorlev (levoketoconazole), Strongbridge Biopharma’s oral investigational therapy for endogenous Cushing’s syndrome, resulted in sustained improvements in cortisol and glycemic control in patients with Cushing and diabetes. This was the result of a subgroup analysis of the data from the phase 3 SONICS study.
“Mellitus Diabetes [type 1 diabetes] is one of the most common complications associated with excessive cortisol levels in people with Cushing’s syndrome, ”said Dr. Fredric Cohen, Strongbridge’s chief medical officer, in a press release.
“The results of the SONICS study provide important evidence that will help further characterize the potential clinical benefit and role of Recorlev as an important treatment option for patients with Cushing’s syndrome,” added Cohen.
The results of 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 concurrent diseases, including diabetes, which is characterized by poor blood sugar control.
Chronically high levels of cortisol are known to raise blood sugar levels. Treatment of diabetes associated with Cushing’s syndrome requires tight control of both blood sugar and cortisol.
Recorlev lowers cortisol by blocking an enzyme that is needed for the last step of its production in the adrenal glands, which the kidneys stop.
The SONICS open-label study (NCT01838551) assessed Recorlev’s ability to normalize participants’ mean 24-hour cortisol levels (mUFC) over a period of six months of maintenance therapy without increasing the dose during this period.
The study included a dose-titration phase and a six-month maintenance phase, followed by a six-month extended assessment to better understand the safety, efficacy and tolerability of the experimental therapy.
The study results, announced in 2018 for the main study and in 2019 for its extension, showed that Recorlev is well tolerated, can normalize urinary cortisol levels, and lower the risk of heart disease, one of the study’s key secondary goals.
A more recent analysis of the study results published last year also showed that Recorlev was able to alleviate symptoms of Cushing’s syndrome and depression while improving the quality of life for patients, especially in female patients.
The new results of the subgroup analysis focused on the effects of Recorlev in patients with Cushing and diabetes.
Of the 94 people with endogenous Cushing enrolled at SONICS, 36 (38.3%) had diabetes. Among them, 28 (77.8%) were in the maintenance phase of the study, along with 49 (84.5%) non-diabetic patients.
Of the 21 people with diabetes and 40 without this phase, 13 (62%) diabetics and 16 (40%) non-diabetics achieved normal mUFC levels.
Other markers of glycemic control and heart health also improved over the course of the study, generally more in diabetic than in non-diabetic. The researchers were able to rule out the effects of changes in diabetics that remained stable throughout treatment.
At the end of the maintenance phase, the hemoglobin A1c level – the proportion of hemoglobin that is bound to glucose or blood sugar – was from 6.9% to 6.2% in diabetics and from 5.5% to 5 in patients without diabetes, 3% down.
The mean fasting blood sugar level also fell from 123.4 mg / dl to 104.9 mg / dl in diabetics and from 92.1 mg / dl to 84.0 mg / dl in diabetics without diabetes.
With all of these measures, cases of deterioration were rare, investigators found. Other key heart health measures also improved in small but still significant ways.
Low-density lipoprotein cholesterol (commonly referred to as “bad” cholesterol), weight, and body mass index decreased in similar rates in people with and without diabetes.
The incidence of undesirable side effects was roughly equal between the two groups (97.2% of patients with diabetes and 98.3% of non-diabetics), with nausea and headache being the most common occurrences overall. Side effects that were more common in diabetics included nausea (58.3%), vomiting (19.4%), and urinary tract infections (16.7%), none of which led to the study being discontinued.
One non-diabetic patient withdrew due to a headache. According to the company, none of the side effects appeared to be dose-related and rarely interfered with treatment.
Although this subgroup analysis was classified as “exploratory” and still requires “validation by an independent study”, it found that “treatment with [Recorlev] led to a sustained normalization of mUFC and an improvement in blood sugar control, which was more pronounced in patients with [diabetes]”Wrote the researchers.
Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. Since then he has worked as a journalist and science journalist, dealing with topics ranging from rare diseases to the interface between environmental science and social justice. He currently lives in Long Beach, California.
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Joana holds a BSc in Biology, an MSc in Evolutionary and Developmental Biology and a PhD in Biomedicine from Universidade de Lisboa, Portugal. Her work focused on the influence of non-canonical Wnt signals on the collective behavior of endothelial cells – cells that made up the lining of blood vessels – found in the umbilical cord of newborns.
