Clinical Trials Testing Osilodrostat for the Treatment of Cushing’s Disease

Maria Fleseriu, MD, Director of the Pituitary Center at Oregon Health and Science University, discusses clinical trials testing osilodrostat for the treatment of Cushing’s disease.
Cushing’s disease is a rare condition characterized by elevated levels of the cortisol hormone secreted by a tumor in the pituitary gland. It is characterized by signs and symptoms that may include:
- Weight gain around the trunk and in the face
- Stretch marks
- Easy bruising
- A hump on the upper back
- Muscle weakness
- Tiredness
- Thin bones that are prone to fracture (osteoporosis)
- Mood disorders
- Memory problems
- Increased risk of infections
- High blood pressure
- Diabetes
- Women may have irregular menses and a lot of hair in the body (hirsutism).
Cushing’s disease occurs when a benign pituitary tumor (adenoma) or pituitary hyperplasia causes the adrenal glands to produce large amounts of cortisol. Some cases are caused by somatic genetic changes in the AIP and the GNAS genes. Rarely, Cushing’s disease can be inherited, either as an isolated condition or as part of a genetic syndrome, but most cases are sporadic.
Current management begins with a surgery to remove the tumor. However, this surgery does not work on every patient and recurrence rates are around 30-35%. Medical therapies are used in the case of unsuccessful surgeries.
210 patients were analyzed in the LINC3 and LINC4 clinical trials testing the safety and efficacy of osilodrostat in patients with Cushing disease. Osilodrostat, an 11β-hydroxylase inhibitor, blocks the adrenal secretion of cortisol and is taken twice a day, orally. Results observed in the trials provide adequate evidence of the benefits of osilodrostat in treating Cushing’s disease.
Prior to this treatment, 83% of patients enrolled had hypertension. The severity of hypertension decreased over time of treatment and was maintained long term. The majority of patients with high blood pressure at baseline were normal at week 12 and 27% of patients that took medications for blood pressure at baseline were able to reduce dosage or stop altogether. However 25% had to increase doses, showcasing the importance of personalized medicine and finding the right treatment combinations that will work for each individual patient. Prior to treatment, 40% of patients enrolled had diabetes. The severity decreased over treatment time, with evidence of improved glycemic control. Of those with A1C greater than 6.5 at baseline, 59% had A1C less than 6.5 at week 12, and 62% had A1C less than 6.5 at week 72. Similar results in regard to medication dosage were observed as with hypertension.
Chapters:
Cushing's Disease Overview 00:00
Osilodrostat Clinical Trials 2:18