Cushing’s disease (or Cushing disease) occurs when a benign pituitary growth or tumor leads to the overproduction of adrenocorticotropic hormone (ACTH). As ACTH is overproduced, the body also begins overproducing cortisol, a type of hormone. This overproduction eventually leads to the symptoms and manifestation of Cushing’s disease. Throughout the Phase 2 LINC-2 clinical study, as well as 7+ years of the trial’s extension phase, researchers sought to understand the benefits of Isturisa (osilodrostat) for those with Cushing’s disease.
Evaluating Isturisa
According to Cushing’s Disease News, the study evaluated the safety, efficacy, and tolerability of Isturisa in individuals with Cushing’s disease between the ages of 18 and 75. Findings from the first portion of the study show that:
- Isturisa treatment helped reduce urinary free cortisol (UFC) levels and return them to normal for 11 of the 12 initially dosed patients. UFC signals how much cortisol is active in the body.
- Next, a protocol amendment added some patients to the trial. These 19 patients were treated with up to 30mg Isturisa 2x each day. By 22 weeks, the overall response rate was 78.9%.
- While Isturisa was relatively well-tolerated, some adverse reactions did occur. These included nausea, fatigue and lethargy, diarrhea, and adrenal insufficiency.
Those who felt that Isturisa benefited them were given the opportunity to enroll in the extension phase, the results of which were published in Pituitary. Altogether, 16 participants enrolled in the extension phase, with 14 completing one year and eight completing a second year. Findings from this portion of the study show that:
- By week 70, there was an overall response rate of 81.3% in terms of UFC reductions. Of these patients, 12 had a complete response.
- The overall response rate varied from 50-88% up to month 70 of the trial.
- While Cushing’s disease often comes with progressive cardiovascular symptoms, Isturisa helped to control these during the course of the study.
- At the last trial measurement, 63.2% of patients had either partially or completely responded to treatment.
What is Cushing’s Disease?
An estimated 10-15 out of every 1 million people worldwide has Cushing’s disease. It is most common in individuals between ages 20 and 50, and more often affects females than males. Cushing’s disease is variable; symptoms and severity vary widely between those affected. Potential symptoms can include:
- Weight gain, particularly around the face and trunk
- Increased risk of bruising
- Osteoporosis
- Fatigue
- Muscle weakness
- Stretch marks
- Changes in mood, such as worsening anxiety and depression
- Difficulties with memory and concentration
- Weakened immune system
- Menstrual irregularities
- Erectile dysfunction
