Last Review Date: 07/01/2022

Date of Origin: 01/04/2022

Dates Reviewed: 01/2022, 04/2022, 05/2022, 07/2022

1. Length of Authorization

Coverage is provided for six months and may be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Fyarro 100 mg vial: 6 vials every 21 days

B. Max Units (per dose and over time) [HCPCS Unit]:

• 300 billable units (300 mg) on days 1 and 8 of every 21-day cycle

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria

• Patient does not have a severe hypersensitivity to rapamycin derivatives (i.e., sirolimus, everolimus, temsirolimus, etc.); AND
• Patient will avoid concomitant therapy with any of the following:
  • Coadministration with P-gp inhibitors and/or strong CYP3A4 inhibitors (e.g., boceprevir, itraconazole, ketoconazole, etc.), if therapy is unavoidable, the patient will be monitored closely for adverse reaction and/or dose modifications will be implemented; AND
    • • • • Coadministration with combined P-gp inducers and/or strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John’s Wort, etc.), if therapy is unavoidable, the patient will be monitored closely for adverse reaction and/or dose modifications will be implemented; AND
          • Coadministration with grapefruit or grapefruit juice; AND
• Therapy will not be administered concurrently with live vaccines and close contact with individuals who have received live vaccines will be avoided; AND
• Patient does not have uncontrolled or symptomatic CNS metastases; AND
• Patient has had no prior treatment with or will not be used in combination with other mTOR inhibitors (i.e., sirolimus, everolimus, temsirolimus, etc.); AND
• Patient does not have lymphangioleiomyomatosis (LAM); AND

Perivascular Epithelioid Cell Tumor (PEComa) † Ф ^1-4

• Used as single agent therapy; AND
  • Patient has locally advanced unresectable or metastatic disease

† FDA-labeled indication; ‡ Compendia approved indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-3

Coverage can be renewed based upon the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy),  performance status, etc. identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: stomatitis, myelosuppression, infections, hypokalemia and hyperglycemia, interstitial lung disease, hemorrhage, azoospermia/oligospermia, severe hypersensitivity reactions, etc.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9999 – Not otherwise classified, antineoplastic drug (Discontinue use on 07/01/2022)

• J9331 – Injection, sirolimus protein-bound particles, 1 mg; 1 billable unit = 1 mg (Effective 07/01/2022)
• C9091 – Injection sirolimus protein-bound particles, 1 mg; 1 billable unit = 1 mg (Discontinue use on 07/01/2022)

NDC:

• Fyarro 100 mg of sirolimus injection, single-use vial: 80803-0153-xx

7. References

1. Fyarro [package insert].  Pacific Palisades, CA; Aadi Bioscience Inc; December 2021. Accessed March 2022.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) sirolimus-albumin bound. National Comprehensive Cancer Network, 2022. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org.  Accessed March 2022.
3. Wagner AJ, Ravi V, Riedel RF, et al. nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. J Clin Oncol. 2021 Oct 12:JCO2101728. doi: 10.1200/JCO.21.01728. [Epub ahead of print].
4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Soft Tissue Sarcoma Version 3.2021. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed March 2022.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A