Effective Date

Date of Origin   

01-01-2025           

10-01-2012

Korlym®

(mifepristone)*

Tablet

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

Limitations of Use: Do not use for the treatment of type 2 diabetes mellitus unreleated to endogenous Cushing's syndrome.

* - generic available

1

Cushing's Syndrome

Cushing's syndrome is pathologic hypercortisolism caused by excessive adrenocorticotropic hormone (ACTH) production or autonomous adrenal production of cortisol. This potentially lethal disorder is associated with significant comorbidities including hypertension, diabetes, coagulopathy, cardiovascular disease, infections, and fractures. As a result, even after cure of hypercortisolism, mortality rates may be increased. Because of this it is important to make the diagnosis as early in the disease course as possible to prevent additional morbidity and residual disease. Signs and symptoms of Cushing’s syndrome are broad and often common among the general population such as obesity, depression, diabetes, hypertension, or menstrual irregularities. Some features are more discriminatory and unique to Cushing’s syndrome such as reddish-purple striae, plethora, proximal muscle weakness, bruising with no obvious trauma, and unexplained osteoporosis.(3)

Guidelines recommend a multidisciplinary team, including an endocrinologist, providing education and treatment options to the patient. Goals of treatment in Cushing’s syndrome include reversing the patient's clinical features, normalizing biochemical changes with minimal morbidity, and sustained control without recurrence. Surgical resection of the causal lesion(s) is the first-line approach. When surgery is delayed, contraindicated, or unsuccessful, second-line treatments, including medical therapy, bilateral adrenalectomy, and radiation therapy, must be considered. Glucocorticoid antagonists, such as mifepristone, are suggested in patients with diabetes or glucose intolerance who are not surgical candidates or who have persistent disease after surgery.(2)

The American Diabetes Association defines impaired glucose tolerance (glucose intolerance) in prediabetes as plasma glucose of 140 mg/dL to 199 mg/dL (7.8 mmol/L to less than 11.1 mmol/L), and in diabetes as plasma glucose of greater than or equal to 200 mg/dL (11.1 mmol), after the oral glucose tolerance test (OGTT). The OGTT is a two-hour test that checks plasma glucose levels before and 2 hours after drinking a glucose-containing drink.(4)

Efficacy

The safety and efficacy of Korlym in the treatment of endogenous Cushing’s syndrome was evaluated in an uncontrolled, open-label, 24-week, multicenter clinical study. The study enrolled 50 subjects with clinical and biochemical evidence of hypercortisolemia despite prior surgical treatment and radiotherapy. The reasons for medical treatment were failed surgery, recurrence of disease, and poor medical candidate for surgery. Patients belonged to one of two cohorts: a diabetes cohort or a hypertension cohort. While results in the hypertension cohort showed no changes in mean systolic and diastolic blood pressures at the end of the trial, the diabetes cohort showed improvements in glucose response [defined as a greater than or equal to 25% reduction from baseline in glucose area under the curve (AUC) in standard oral glucose tolerance test] in 60% of patients, and reduction in glycated hemoglobin (HbA1c) in all patients.(1)

Safety

Mifepristone has a boxed warning for pregnancy termination. Mifepristone has potent antiprogestational effects and will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with mifepristone, or if the treatment is interrupted for more than 14 days in females of reproductive potential.(1)

Mifepristone is contraindicated in:(1)

• Pregnancy
• Patients taking drugs metabolized by CYP3A such as simvastatin, lovastatin, and CYP3A4 substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus
• Patients receiving systemic corticosteroids for lifesaving purposes (e.g., immunosuppression after organ transplantation)
• Women with a history of unexplained vaginal bleeding or with endometrial hyperplasia with atypia or endometrial carcinoma
• Patients with known hypersensitivity to mifepristone or to any of the product components

1

Korlym prescribing information. Corcept Therapeutics Inc. April 2024.

2

Nieman L, Biller B, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015;100:2807–2831.

3

Nieman, Lynnette K. Recent Updates on the Diagnosis and Management of Cushing’s Syndrome. Endocrinology and Metabolism. 2018 Jun;33:139-146. doi: 10.3803/EnM.2018.33.2.139.

4

American Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Gaglia, J. L., Hilliard, M. E., Johnson, E. L., Khunti, K., Lingvay, I., Matfin, G., McCoy, R. G., Perry, M. L., Pilla, S. J., Polsky, S., Prahalad, P., Pratley, R. E., … Gabbay, R. A. (2023, December 11). 2. diagnosis and classification of diabetes: Standards of care in diabetes-2024. American Diabetes Association. https://diabetesjournals.org/care/article/47/Supplement_1/S20/153954/2-Diagnosis-and-Classification-of-Diabetes.

Korlym

mifepristone tab

300 MG

M ; N ; O ; Y

O ; Y

Korlym

mifepristone tab

300 MG

120

Tablets

30

DAYS

Korlym

mifepristone tab

300 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Korlym

mifepristone tab

300 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. The patient has a diagnosis of Cushing’s syndrome AND
      1. If the patient has an FDA labeled indication, then ONE of the following:
         1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
         2. There is support for using the requested agent for the patient’s age for the requested indication AND
      2. ONE of the following:
         1. The patient has type 2 diabetes mellitus OR
         2. The patient has glucose intolerance as defined by a 2-hr glucose tolerance test plasma glucose value of 140-199 mg/dL AND
      3. ONE of the following:
         1. The patient has had an inadequate response to surgical resection OR
         2. The patient is NOT a candidate for surgical resection AND
2. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

2. 1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. There is support for the use of the requested brand agent over the generic equivalent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. The requested dose does NOT exceed 20 mg/kg/day

Length of Approval: 6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: Patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

3. 1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. There is support for the use of the requested brand agent over the generic equivalent AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. The requested dose does NOT exceed 20 mg/kg/day

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit

Length of Approval: up to 12 months