Effective Date

Date of Origin 

1/1/2023

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: Should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing’s syndrome

1

Cushing's Syndrome

Cushing’s syndrome is an endocrine disorder caused by excessive and prolonged secretion of cortisol. Whereas the most common cause is from corticosteroids (known as exogenous Cushing’s syndrome), endogenous Cushing’s syndrome may be caused by either excess adrenocorticotropin hormone (ACTH) secretion (from a pituitary or other ectopic tumor) or independent adrenal overproduction of cortisol. Features of Cushing’s syndrome include weight gain, fatigue, muscle weakness, high blood pressure, depression, cognitive impairment (e.g., decreased concentration, impaired memory), easy bruising, hyperpigmentation, loss of libido, hirsutism, acne, menstrual disorders, and diabetes/glucose intolerance.(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 reversal of clinical features, normalization of biochemical changes with minimal morbidity, and long-term 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 (greater than 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, 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 (1)

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.

Safety (1)

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.

Mifepristone is contraindicated in:

• 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. November 2019.

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 L, Biller B, et al. Diagnosis of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93(5):1526-1540.

4

American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes. Clin Diabetes;40(1):10-38.

KORLYM*mifepristone tab

300 MG

M ; N ; O ; Y

N

273040500003

KORLYM*mifepristone tab

300 MG

120.0

TABS

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. The patient has a diagnosis of Cushing’s syndrome AND
2. ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
3. 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
4. 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
5. 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
6. The patient does NOT have any FDA labeled contraindications to the requested agent AND
7. 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.

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 AND
2. The patient has had clinical benefit with the requested agent 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: 12 months

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

QL with PA

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. ALL of the following:
   1. The requested quantity (dose) is greater than the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose AND
   3. 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: Initial: 6 months; Renewal: 12 months