What Ispurisa (Osilodrostat) Treats
Ispurisa (osilodrostat) is FDA-approved for the treatment of Cushing's disease in adults who cannot undergo pituitary surgery or for whom surgery has failed to achieve remission. 1, 2
Primary Indication
Osilodrostat treats endogenous Cushing's disease (CD) caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. 1, 2 The drug is specifically indicated when:
- Pituitary surgery is contraindicated 1
- Surgical intervention has failed to achieve remission 1
- Disease recurrence occurs after initial surgical remission 1
Mechanism and Clinical Effects
Osilodrostat functions as a potent inhibitor of 11-β hydroxylase, the enzyme responsible for the final step in cortisol synthesis. 1, 2 This mechanism rapidly and consistently reduces supraphysiological cortisol levels in patients with CD. 2
Demonstrated Clinical Benefits
The drug provides improvements across multiple disease manifestations:
- Normalization of 24-hour urinary free cortisol (UFC) - the primary endpoint showing 86% response rate versus 29% with placebo (P < 0.001) 2
- Improved glycemic control in patients with cortisol-induced diabetes 1
- Blood pressure reduction - often allowing reduction in antihypertensive medications 1, 3
- Weight loss and reduction in central adiposity 1
- Enhanced quality of life and decreased depression symptoms 1
Regulatory Status
Osilodrostat received FDA approval in 2020 for adult Cushing's disease and European Medicines Agency approval for Cushing's syndrome. 4 The drug is marketed as Isturisa in the United States and Europe. 1
Pediatric Considerations
Osilodrostat is not currently approved for pediatric use, though a Phase II trial (NCT03708900) is evaluating its safety and efficacy in patients under 18 years of age. 4 The estimated completion date for this pediatric trial is 2023. 4
Important Clinical Distinctions
Osilodrostat treats Cushing's disease specifically (pituitary-driven hypercortisolism), not other forms of hypercortisolism such as adrenal adenomas or ectopic ACTH syndrome, though it has been studied in these contexts. 3 The drug addresses the biochemical consequences of excess cortisol production regardless of etiology, but its formal indication remains Cushing's disease. 1, 2