The FDA approved osilodrostat (Isturisa, Recordati) for a new indication as a second-line treatment for adults with endogenous Cushing syndrome in April 2025. This oral medication, which inhibits cortisol synthesis, was previously approved for Cushing disease and now extends treatment options for patients unable to undergo surgery or those for whom surgery was unsuccessful.
Cushing syndrome, caused by excessive cortisol production, leads to complications including weight gain, high blood sugar, high blood pressure, osteoporosis, fragile skin, and muscle weakness. The expanded approval addresses a critical need for patients with this rare endocrine disorder.
Relacorilant Shows Promise in Phase III Trials
The investigational drug relacorilant, a selective glucocorticoid receptor modulator currently under FDA review, demonstrated significant benefits in managing Cushing syndrome symptoms. In two Phase III trials—GRACE and GRADIENT—relacorilant improved key clinical parameters in patients with adrenal hypercortisolism.
Pooled results showed patients treated with relacorilant experienced notable decreases in systolic and diastolic blood pressure (-10.1 mm Hg and -6.3 mm Hg, respectively) as measured by 24-hour ambulatory monitoring, compared to placebo, which showed slight increases (1.5 mm Hg and 2.2 mm Hg). The treatment also reduced fasting glucose levels and body weight. These findings were presented by Dr. Corin Badiu of the Carol Davila University of Medicine and Pharmacy and the National Institute of Endocrinology in Romania.
The FDA accepted the New Drug Application (NDA) for relacorilant in March 2025, backed by results from the Phase III GRACE trial (NCT03697109) and the confirmatory GRADIENT trial (NCT04308590). Relacorilant is a selective cortisol modulator that targets the glucocorticoid receptor.
Long-Term Safety and Efficacy Data
Corcept Therapeutics announced positive long-term results from its Phase III study evaluating relacorilant for endogenous hypercortisolism in December 2024. The treatment demonstrated sustained cardiometabolic benefits and was well tolerated for up to six years. The open-label extension study included 116 participants who had previously completed the GRACE or GRADIENT studies or a Phase II clinical trial in hypercortisolism.
Expanding Treatment Options
A study from the Netherlands suggests that sequential treatment with ketoconazole to reduce cortisol levels, followed by octreotide to maintain control, may benefit certain individuals with mild Cushing disease. Among three patients who responded to this approach, two showed normalized cortisol levels along with improvements in weight, waist size, and blood pressure. Ketoconazole, sold as Ketoconazole Esteve in Europe, is approved there for Cushing disease but not in the U.S.
Robust Pipeline Development
The Cushing syndrome pipeline constitutes over 4 key companies continuously working toward developing more than 4 treatment therapies. Companies working in the treatment market include Crinetics Pharmaceuticals, AstraZeneca, Novartis, Sparrow Pharmaceuticals, Corcept Therapeutics, RECORDATI GROUP, Cortendo AB, and HRA Pharma.
Emerging therapies such as CRN-04894, AZD4017, SOM230, SPI 62, Relacorilant, osilodrostat, Levoketoconazole, metyrapone, evoketoconazole, and SPI-62 are expected to have significant impact on the Cushing syndrome market.
Sterotherapeutics initiated a Phase II clinical trial for its investigational drug ST-002 in February 2025. The study aims to evaluate the drug's efficacy, safety, and tolerability in affected individuals and will be conducted across multiple clinical sites in Europe.
Sparrow Pharmaceuticals completed the Phase 2 RESCUE trial evaluating clofutriben, a potent and selective HSD-1 inhibitor, for endogenous Cushing syndrome in October 2024. All eligible patients who completed the trial chose to continue treatment under an open-label extension protocol.
Market Dynamics
The entrance of novel therapies and increased research and development activities are driving Cushing syndrome market growth. However, high treatment costs, strict regulatory policies, and lack of awareness among people create obstacles in market growth.
The pipeline includes products categorized under various routes of administration including oral, parenteral, intravenous, subcutaneous, and topical formulations. Molecule types span monoclonal antibodies, peptides, polymers, small molecules, and gene therapy approaches.
