Drug and Biologic Coverage Policy Effective Date ............................................ 1/1/2021 Next Review Date… ..................................... 1/1/2022 Coverage Policy Number ............................... IP0092 Mifepristone (Korlym®) Table of Contents Related Coverage Resources Overview .............................................................. 1 Coverage Policy ................................................... 1 Reauthorization Criteria ....................................... 2 Authorization Duration ......................................... 2 Conditions Not Covered....................................... 2 Background .......................................................... 3 References .......................................................... 4 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Overview This policy supports medical necessity review for mifepristone (Korlym®) Coverage Policy Mifepristone (Korlym®) is medically necessary when ALL of the following are met: 1. Individual is 18 years of age or older 2. Mifepristone (Korlym®) is prescribed by or in consultation with an endocrinologist or a physician who specializes in the treatment of Cushing’s syndrome 3. Individual has ONE of the following: a. Documented Endogenous Cushing’s Syndrome and BOTH of the following: • Mifepristone (Korlym®) is being used to control hyperglycemia secondary to hypercortisolism in individuals who have type 2 diabetes mellitus or glucose intolerance • According to the prescriber, the individual is not a candidate for surgery or surgery has not been curative Page 1 of 4 Coverage Policy Number: IP0092 b. Documented Endogenous Cushing’s Syndrome with hyperglycemia - Individual Awaiting Surgery • Mifepristone (Korlym®) is being used to control hyperglycemia secondary to hypercortisolism in individuals who have type 2 diabetes mellitus or glucose intolerance c. Documented Endogenous Cushing’s Syndrome - Individual Awaiting Response After Radiotherapy • Mifepristone (Korlym®) is being used to control hyperglycemia secondary to hypercortisolism in individuals who have type 2 diabetes mellitus or glucose intolerance When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy. Note: Receipt of sample product does not satisfy any criteria requirements for coverage. Documentation: When documentation is required, the prescriber must provide written documentation supporting the trials of these other agents. Documentation may include, but is not limited to, chart notes, prescription claims records, and/or prescription receipts Reauthorization Criteria Mifepristone (Korlym®) is considered medically necessary for continued use when initial criteria are met AND there is documentation of beneficial response (such as an improvement in fasting glucose, oral glucose tolerance, or hemoglobin A1c results). Authorization Duration Initial and reauthorization is as follows unless otherwise stated: • Endogenous Cushing’s Syndrome: Approve for 1 year • Endogenous Cushing’s Syndrome – Individuals Awaiting Surgery: Approve for 6 months • Endogenous Cushing’s Syndrome – Individuals Awaiting Therapeutic Response After Radiotherapy: Approve for 6 months Conditions Not Covered Mifepristone (Korlym®) is considered experimental, investigational or unproven for ANY other use including the following (this list may not be all inclusive): 1. Exogenous (Iatrogenic) Cushing’s Syndrome. Korlym is not indicated in exogenous Cushing’s syndrome. Exogenous Cushing’s syndrome is caused by excessive glucocorticoid administration.12 Therefore, the process to reverse the excessive cortisol exposure is to taper or discontinue the offending drug when possible. 2. Type 2 Diabetes Not Associated with Endogenous Cushing’s Syndrome. Korlym should not be used for the treatment of type 2 diabetes unrelated to endogenous Cushing’s syndrome.1 3. Psychotic Features of Psychotic Depression. Mifepristone has been used to treat the psychotic features of psychotic depression. Individual trials have demonstrated variable efficacy results.3,10-11,15,18 In some of the studies comparing mifepristone with placebo, various statistically significant improvements in psychiatric symptoms have been noted with mifepristone relative to placebo; however, the methodology and statistical analyses of some studies have been questioned.14 Data are inconclusive. Page 2 of 4 Coverage Policy Number: IP0092 Background FDA Approved 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. Limitations of use: Korlym should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing’s syndrome. FDA Recommended Dosing The recommended starting dose is 300 mg orally once daily. Korlym must be given as a single daily dose. Korlym should always be taken with a meal. Patients should swallow the tablet whole. Do not split, crush, or chew tablets. The daily dose of Korlym may be increased in 300 mg increments. The dose of Korlym may be increased to a maximum of 1200 mg once daily but should not exceed 20 mg/kg per day. Increases in dose should not occur more frequently than once every 2-4 weeks. Decisions about dose increases should be based on a clinical assessment of tolerability and degree of improvement in Cushing’s syndrome manifestations. Drug Availability Korlym (mifepristone) is available as 300 mg tablet. OVERVIEW Korlym 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.1 Korlym should not be used for the treatment of type 2 diabetes mellitus unrelated to endogenous Cushing’s syndrome. Mifepristone, the active ingredient in Korlym is also available as Mifeprex® (mifepristone 200 mg tablets) indicated for the medical termination of intrauterine pregnancy through 70 days’ pregnancy.2 Mifeprex is not included in this policy. Mifepristone, the active ingredient in Korlym is a selective antagonist of the progesterone receptor (PR) at low doses and blocks the glucocorticoid type 2 receptor (GR-II) at higher doses.1 Mifepristone has high affinity for the GR-II receptor but little affinity for the GR-I (mineralocorticoid) receptor (MR). In addition, mifepristone appears to have little or no affinity for estrogen, muscarinic, histaminic, or monoamine receptors. Mifepristone acts at the receptor level to block the effects of cortisol, and its antagonistic actions affect the hypothalamic-pituitary-adrenal (HPA) axis in such a way as to further increase circulating cortisol levels while at the same time blocking their effects. Mifepristone and its three active metabolites have greater affinity for the glucocorticoid receptor (100%, 61%, 48%, and 45%, respectively) than either dexamethasone (23%) or cortisol (9%). Endogenous Cushing’s Syndrome Endogenous Cushing’s syndrome is a rare heterogeneous disorder with diverse causes that leads to cortisol excess (hypercortisolism).3 Patients with Cushing’s syndrome exhibit a variety of signs and symptoms such as high blood pressure, diabetes, loss of libido, menstrual disorders, weight gain, hirsutism, acne, easy bruising, purplish skin striae, osteoporosis, muscle weakness, depression