CurrentCentenePolicy CP.PHAR.487

Osilodrostat (Isturisa) — Coverage Criteria

Defines medical necessity criteria, dosing limits, and prior authorization requirements for osilodrostat (Isturisa) for adults with endogenous Cushing's syndrome when surgery is not an option or not curative; applies to Centene-affiliated lines of business including Commercial, HIM, and Medicaid.

Policy Summary

PayerCentene

PolicyOsilodrostat (Isturisa) — Coverage Criteria

Policy CodePolicy CP.PHAR.487

Change TypeRevised indication and labeling language

Effective DateSep 1, 2020

Next Review Date

Key ActionSubmit prior authorization with documentation that the patient has Cushing's syndrome, is ≥18 years, and either surgery was not curative or the patient is not eligible for surgery.

SourceLink

POLICY UPDATE CHANGES

FDA Approved Indication(s) revised to expand approval from Cushing's disease to Cushing's syndrome and criteria modified to reflect updated labeling language.

18+Minimum patient age (years)

60 mg/dayMax total daily dose

30 mg BIDMax per dose (label)

6 moInitial approval

12 mo

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Coverage Criteria for Osilodrostat (Isturisa)

Initial Therapy

Covered when ALL of the following are met:

Initial Approval Criteria for Cushing's Syndrome: 1. Diagnosis of Cushing's syndrome; 2. Prescribed by or in consultation with an endocrinologist; 3. Age ≥ 18 years; 4. Member meets one of the following: a) Surgery has not been curative; b) Member is not eligible for surgery; 5. Dose does not exceed 30 mg twice daily.

Approval duration: 6 months

Continued Therapy

Covered when ALL of the following are met:

Continued Therapy Criteria for Cushing's Syndrome: 1. Member meets one of the following: a) Currently receiving medication via Centene benefit or previously met initial approval criteria; b) Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy (see Appendix D); 3. If request is for a dose increase, new dose does not exceed 30 mg twice daily.

Approval duration: 12 months; Maximum total daily dose: 60 mg/day (maximum recommended maintenance dosage: 30 mg twice daily).

Other Diagnoses / Off-label Requests

Other Indications: 1. If the drug has undergone a label change within the last 6 months that is not yet reflected in this policy, follow the referenced formulary/non‑formulary policies for the applicable line of business; OR 2. If the requested use is not specifically listed in Section III (Diagnoses/Indications for which coverage is NOT authorized) and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business (see CP.CPA.09, HIM.PA.154, CP.PMN.53).

See referenced policies per line of business

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy for the member's line of business (see CP.CPA.09, HIM.PA.154, CP.PMN.53).

Use of this medication for non‑FDA approved indications without sufficient supporting clinical documentation is considered not authorized and may be denied per the applicable off‑label use policy. Providers must submit clinical records, such as office notes and relevant test results, to support off‑label requests per the referenced policies.

Product Codes and Monitoring

NDC / Product codesNDC

NDC	Not specified in document

inv-07: 24-hour urinary free cortisol (UFC) — monitoring frequency, normal ranges, interpretation guidance

Monitoring frequency during titrationObtain at least two 24-hour urine free cortisol (UFC) collections every 1–2 weeks while titrating dose until adequate clinical response is maintained.

Monitoring frequency after maintenanceOnce maintenance dose is achieved, monitor cortisol levels at least every 1–2 months or as clinically indicated.

Titration schedule relevant to monitoringInitial titration: increase by 1–2 mg twice daily no more frequently than every 2 weeks; if tolerating 10 mg twice daily and UFC remains above normal, may increase by 5 mg twice daily every 2 weeks — monitor UFC collections accordingly.

Interpretation guidance for low UFCDecrease or temporarily discontinue therapy if UFC falls below target range or there is a rapid decrease in cortisol levels; assess for hypocortisolism and consider glucocorticoid replacement if symptomatic.

Target for response assessmentUse serial 24-hour UFC reductions and clinical improvement in signs and symptoms to determine adequacy of response (see Appendix D for response timing).

Prior Authorization and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Isturisa (osilodrostat) for the treatment of Cushing's syndrome. Requests must include supporting clinical documentation and be consistent with the policy's initial or continued therapy criteria. Prescriptions should be written by or in consultation with an endocrinologist as specified in the policy.

Prior authorization required for Isturisa
Prescriber: endocrinologist or in consultation with an endocrinologist
Maximum dose: 30 mg twice daily

Step Therapy

No step therapy or prerequisite medications are required prior to initiation of Isturisa per this policy. Authorization decisions are based on meeting the initial or continued therapy clinical criteria rather than failure of other medical therapies.

Background on Osilodrostat

Osilodrostat (Isturisa) is an oral cortisol synthesis inhibitor indicated for adults with endogenous hypercortisolemia associated with Cushing's syndrome when surgery is not an option or has not been curative. Treatment effect is typically assessed by reduction in 24‑hour urinary free cortisol (UFC) and clinical improvement; maximal UFC reductions are often seen by about 2 months. Dosing is initiated at low dose with titration and monitoring per labeling, with a maximum recommended total daily dose of 60 mg/day (not to exceed 30 mg twice daily for initial requests).

Definitions and Response Metrics

inv-13: Response — treatment response definition and related monitoring endpoints

Definition of treatment responseReduction in 24-hour urinary free cortisol (UFC) levels and/or improvement in signs or symptoms of Cushing's syndrome; maximum UFC reduction typically seen by two months of treatment.

Primary monitoring endpointChange in 24-hour UFC from baseline using serial collections to document biochemical response.

Clinical endpointsImprovement in signs and symptoms of Cushing's syndrome alongside UFC reduction to support continued therapy decisions.

inv-14: UFC — urinary free cortisol reference ranges and interpretation notes

Sampled adult reference range (U.S. labs)24-hour UFC adult reference values range from 3 to 64 mcg/24 h across sampled U.S. laboratories (Mayo Clinic, LabCorp, Quest).

Levels suggesting Cushing's syndrome