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Label indication KORLYM (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. FDA label
Also known as Mifepristone daily, CORLUX®
Mifepristone · 12 trials · 15 indications
Safety was assessed at all visits and adverse events were recorded.
Responder is defined as subject with a decrease greater than or equal to 25% in area under the curve for glucose on 2-hour oral glucose test from baseline to week 24 or last visit, for Cushing's patients with type-2 diabetes mellitus/impaired glucose tolerance.
Responder is defined as subject with a decrease greater than or equal to 5mm Hg in diastolic blood pressure from baseline to week 24 or last visit.
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Measured with the monthly version of the CAPS-5 (Clinician Administered PTSD scale) in patients with treatment-resistant PTSD. Minimum and maximum score range from 0-80, with higher scores indicating greater PTSD symptom severity.
In the dose escalation phase: MTD time frame is within 28 days of first dose (Cycle 1)
| Arm | Type | Description |
|---|---|---|
| mifepristone | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | - |
| mifepristone 600 mg | EXPERIMENTAL | - |
| matching placebo | PLACEBO_COMPARATOR | - |
| mifepristone 300 mg | EXPERIMENTAL | - |
| placebo | PLACEBO_COMPARATOR | - |
| mifepristone 1200 mg | EXPERIMENTAL | - |
| Mifepristone and Eribulin in combination | EXPERIMENTAL | Single Arm |
| Name | Type | Description |
|---|---|---|
| Mifepristone | DRUG | mifepristone at doses from 300mg/day up to 1200mg/day |
| placebo | DRUG | - |
| mifepristone matched placebo | DRUG | daily for 7 days |
| mifepristone 600 mg | DRUG | mifepristone 600 mg daily for 7 days |
| mifepristone 1200 mg | DRUG | mifepristone 1200 mg daily for 7 days |
| matching placebo | DRUG | daily for 7 days |
| Mifepristone 1200 mg daily | DRUG | Oral tablets |
| Mifepristone and Eribulin in combination | DRUG | Single Arm, Two Parts Part 1: Dose Escalation Phase to determine MTD and RP2D in up to 20 patients Part 2: Dose Expansion Phase at RP2D in 20 patients |
Inclusion Criteria: 1. Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or ACTH independent etiologies including: * Cushing's Disease that (more than one may apply) * has recurred after primary pituitary surgery * has persisted despite pituitary sur...
Mifepristone is being studied in breast cancer, Cushing's disease, Cushing's syndrome, major depressive disorder, treatment-resistant PTSD, and weight-gain prevention. Corcept Therapeutics Incorporated is developing it across these indications, with the most advanced work in Cushing's syndrome and depression. It is a small molecule and remains investigational in these settings.
Mifepristone targets the progesterone receptor (PGR) and the glucocorticoid receptor (NR3C1), acting as an antagonist at both. By blocking these nuclear receptors, it interferes with hormone-driven signaling relevant to its studied indications, including Cushing's syndrome, where glucocorticoid receptor blockade is the intended mechanism.
Corcept Therapeutics Incorporated, which trades under the ticker CORT, is the developer of mifepristone for the indications in its pipeline. The company has sponsored trials in Cushing's syndrome, depression, PTSD, and breast cancer, and holds the development program referenced here.
Mifepristone is in Phase 1 development according to the program data, and it is investigational rather than approved for the indications listed. Its trial record spans Phase 1 through Phase 3 studies, with six total trials, five completed and one currently active.
The active trial is NCT06689254, the REVERSE study of glucocorticoid receptor antagonism in treatment-resistant PTSD, recruiting 60 participants in the Netherlands. Completed studies include NCT05217758 in major depressive disorder with childhood trauma, NCT02014337 combining mifepristone with eribulin in solid tumors, and NCT01371565 in Cushing's syndrome.