Clinical Policy: Osilodrostat (Isturisa) Form

Page 1 of 6 Clinical Policy: Osilodrostat (Isturisa) Reference Number: CP.PHAR.487 Effective Date: 09.01.20 Last Review Date: 08.25 Line of Business: Commercial, HIM, Medicaid Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description
Osilodrostat (Isturisa®) is a cortisol synthesis inhibitor.

FDA Approved Indication(s) Isturisa is indicated for the treatment of endogenous hypercortisolemia in adults with Cushing’s syndrome (CS) for whom surgery is not an option or has not been curative.

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

CLINICAL POLICY Osilodrostat

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2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

   B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.

   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CS: Cushing’s syndrome FDA: Food and Drug Administration UFC: urinary free cortisol

Page 3 of 6 Appendix B: Therapeutic Alternatives
Not applicable

Appendix C: Contraindications/Boxed Warnings None reported

Appendix D: General Information • Treatment response for CS may be defined as reduction in 24-hour urinary free cortisol (UFC) levels and/or improvement in signs or symptoms of the disease. Maximum UFC reduction is typically seen by two months of treatment.
• Across sampled U.S. laboratories (Mayo Clinic Laboratories, LabCorp, Quest Diagnostics), 24-hour UFC adult reference values range from 3 to 64 mcg/24 h. The American Association of Neurological Surgeons notes that UFC levels higher than 50- 100 mcg/24 h in adults suggest the presence of CS. In this context, the Endocrine Society notes that 24-hour UFC levels may range from more than 5 times normal in severe cases to as low as 1.5 times normal in relatively mild cases.

V. Dosage and Administration
Indication Dosing Regimen Maximum Dose CS Recommended Dosage, Titration, and Monitoring • Initiate dosing at 2 mg orally twice daily, with or without food. • Initially, titrate the dosage by 1 to 2 mg twice daily, no more frequently than every 2 weeks based on the rate of cortisol changes, individual tolerability and improvement in signs and symptoms of CS. If a patient tolerates Isturisa dosage of 10 mg twice daily and continues to have elevated 24-hour urine free cortisol (UFC) levels above upper normal limit, the dosage can be titrated further by 5 mg twice daily every 2 weeks. Monitor cortisol levels from at least two 24-hour urine free cortisol collections every 1-2 weeks until adequate clinical response is maintained. • The maintenance dosage of Isturisa is individualized and determined by titration based on cortisol levels and patient’s signs and symptoms. • The maintenance dosage varied between 2 mg and 7 mg twice daily in clinical trials. The maximum recommended maintenance dosage of Isturisa is 30 mg twice daily. • Once the maintenance dosage is achieved, monitor cortisol levels at least every 1-2 months or as indicated. Dosage Interruptions and Modifications • Decrease or temporarily discontinue Isturisa if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms 60 mg/day

CLINICAL POLICY Osilodrostat

Page 4 of 6 Indication Dosing Regimen Maximum Dose of hypocortisolism. If necessary, glucocorticoid replacement therapy should be initiated. • Stop Isturisa and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency. • If treatment is interrupted, re-initiate Isturisa at a lower dose when cortisol levels are within target ranges and patient symptoms have been resolved.

VI. Product Availability
Tablets: 1 mg, 5 mg

Reviews, Revisions, and Approvals Date P&T Approval Date 3Q 2021 annual review: no significant changes; modified HIM.PHAR.21 to HIM.PA.154; references reviewed and updated. 04.05.21 08.21 3Q 2022 annual review: no significant changes; references reviewed and updated. 05.04.22 08.22 Template changes applied to other diagnoses/indications and continued therapy section. 10.03.22

3Q 2023 annual review: no significant changes; references reviewed and updated.

04.14.23 08.23 3Q 2024 annual review: no significant changes; references reviewed and updated. 05.14.24 08.24

CLINICAL POLICY Osilodrostat

Page 5 of 6 Reviews, Revisions, and Approvals Date P&T Approval Date 3Q 2025 annual review: RT4: revised FDA Approved Indication(s) to reflect expanded approval in Cushing’s syndrome (previously only Cushing’s disease) and modified criteria to reflect updated labeling language; removed 10 mg tablet strength as it is no longer on market; references reviewed and updated. 04.28.25 08.25

CLINICAL POLICY Osilodrostat

Page 6 of 6 Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited.
Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note:
For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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