Signifor Normalizes Cortisol Levels in Cushing’s Disease Patients, Real-world Study Shows

In real-life clinical practice, Novartis‘ Signifor (pasireotide) completely or nearly normalizes the levels of cortisol in the urine of patients with mild to moderate Cushing’s disease, a study says.

The study, “The medical treatment with pasireotide in Cushing’s disease: an Italian multicentre experience based on ‘real-world evidence,’ ” was published in the journal Endocrine.

Cushing’s disease is a rare medical condition caused by the excessive production of the adrenocorticotrophic hormone (ACTH) by a tumor in the pituitary gland, which then stimulates the production of the hormone cortisol by the adrenal glands.

While pituitary surgery is the standard treatment for most Cushing’s disease patients, not all achieve remission, and even those who do have a 50% chance their tumor will return.

Signifor is an analogue of somatostatin that has been approved for the treatment of Cushing’s disease patients who are not eligible, or whose disease relapsed after surgery. It works by activating somatostatin receptors and lowering the production of ACTH.

According to findings from a previous Phase 3 clinical trial, up to 1 in 4 Cushing’s patients treated with Signifor saw their urinary cortisol (UC) levels normalize after a treatment period of six months, without significant adverse events.

In this study, a group of Italian researchers set out to evaluate the effects of six months of treatment with Signifor in a group of patients in real-life clinical practice.

The observational study enrolled 32 patients — 25 women and 7 men — between the ages of 21 and 71 years, who started treatment with Signifor at a dose of 600 micrograms (µg) twice a day for a period of six months.

The medication dosage was adjusted throughout the study (to a minimum dose of 300 µg and to a maximum of 900 µg), depending on the patients’ UC levels or presence of treatment side effects. Patients’ hormonal, clinical, and metabolic data were assessed at study start, and after three and six months of treatment with Signifor.

At the beginning of the study, 31 patients had mild to moderate disease severity, and only one had very severe disease. Of the 32 patients initially enrolled in the study, five (15.6%) had to stop treatment due to adverse events; the remaining 27 (84.4%), completed the six-month course of treatment.

Of those who completed the entire course of treatment and had mild to moderate disease severity, 21 achieved normalization or near normalization of their UC levels, corresponding to 67.7% of patients following an “intention-to-treat” approach, which considers all patients initially enrolled, regardless of drop-outs, and 80.8% of patients on a “per-protocol” approach, which takes into account only patients who completed the treatment regimen to which they were originally assigned.

Other clinical parameters, including weight, body mass index, waist circumference, and total and LDL-cholesterol, also decreased significantly after six months of treatment with Signifor. However, the levels of fasting glucose and glycated haemoglobin (hemoglobin molecules bound to glucose) significantly increased, reflecting a high prevalence of diabetes, even after treatment.

The most common adverse events reported in the course of the study were high blood sugar levels (81.2%) followed by gastrointestinal disorders (40.6%), including diarrhea (37.5%), abdominal pain (15.6%), nausea (12.5%), and accumulation of gas in the intestine (3.1%).

“In conclusion, in the real-life clinical practice, pasireotide treatment normalizes or nearly normalizes UC in at least 68% of patients with very mild to moderate disease, with consequent improvement in weight, visceral adiposity and lipid profile, despite the occurrence or deterioration of diabetes in the majority of cases, confirming the usefulness of this treatment in patients with milder disease and without uncontrolled diabetes,” the scientists wrote.