Medical Drug Criteria (MDC)

Policy Num:       P1.001.016
Policy Name:     FYARRO™ (sirolimus protein-bound particles for injectable suspension) (albumin-bound)
Policy ID:          [P1.001.016] [Ac/L/ M+ /P+ ] 

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MDC:NONE

FYARRO™ (sirolimus protein-bound particles for injectable suspension)

(albumin-bound)

Summary

FYARRO™ (nab-sirolimus) is an mTOR inhibitor formulated as sirolimus protein-bound particles (albumin-bound) for IV infusion. FDA Indication: Treatment of adults with locally advanced unresectable or metastatic malignant PEComa. (Approved November 2021). Mechanism: Inhibits the mTOR pathway, a key driver of PEComa progression. Clinical Data: The AMPECT Phase 2 trial showed an objective response rate of ~39%, with durable responses in patients with advanced malignant PEComa.

Objective

Define payer coverage criteria for safe and effective use of FYARRO in malignant PEComa. Standardize initial and renewal requirements. Align coverage with FDA label and NCCN guidelines.

Policy Statements

FYARRO is considered medically necessary for adults with malignant PEComa when all clinical criteria are met.

Adult for Malignant perivascular epithelioid cell tumor, locally advanced unresectable or metastatic

Policy Guidelines

Authorization period: Initial approval up to 6 months.
 
Prescriber requirement: Must be prescribed and managed by an oncologist.
 
Continuation: Allowed if there is evidence of clinical benefit and no unacceptable toxicity.

Background

PEComa: A rare mesenchymal neoplasm with perivascular epithelioid cell morphology, often linked to TSC1/TSC2 mutations and mTOR activation.

Clinical behavior: Aggressive when malignant and unresectable/metastatic.

Therapeutic relevance: FYARRO is the first and only FDA-approved therapy for malignant PEComa.

Regulatory Status

FDA: Approved November 2021.

EMA/International: Approved in EU for malignant PEComa. 

Orphan Drug: Granted in the U.S.

DOSAGE/ADMINISTRATION

For treatment of Malignant perivascular epithelioid cell tumor, locally advanced unresectable or metastatic:  

Dose: 100 mg/m² IV on days 1 and 8 of a 21-day cycle.

Duration: Until disease progression or unacceptable toxicity.

Route: IV infusion over 30 minutes.

REQUIRED MEDICAL INFORMATION

Initial Therapy

a) Perivascular Epithelioid Cell Tumor (PEComa), Malignant: Approve if the patient meets all of the following criteria: 

1.    Patient is ≥ 18 years of age; AND

2.    Patient meets one of the following (i or ii):

i. Patient has locally advanced unresectable disease; OR

ii. Patient has metastatic disease; AND 

3.    Prescribed by an oncologist.

Renewal Approval Criteria 

a)    Continuation of Sirolimus protein-bound particles (Fyarro) meets the definition of medical necessity when ALL of the following criteria are met: 

1.    Member has responded positively to the treatment as determined by the prescribing physician; AND 

2.    Member has not experienced unacceptable toxicity from the drug.
 

EXCLUSION CRITERIA

None beyond standard contraindications (e.g., hypersensitivity).

BENEFIT APPLICATION

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

OTHER CRITERIA

NONE

Rationale

Efficacy: Durable responses in AMPECT trial support FYARRO as a treatment standard for malignant PEComa. Safety: Most common adverse events include mucositis, rash, anemia, hyperlipidemia, and thrombocytopenia. Guideline alignment: NCCN Soft Tissue Sarcoma v2.2025 recommends nab-sirolimus for malignant PEComa (Category 2A).

Supplemental Information

Administration: IV over 30 minutes.
 
Monitoring: CBC, fasting glucose, lipids, renal/hepatic panels prior to and during therapy.
 
Drug interactions: CYP3A4 substrates should be managed carefully

Medicare National Coverage

No NCD specific to nab-sirolimus. Covered under Part B for FDA/NCCN-approved uses.

References

1. Fyarro [package insert]. Pacific Palisades, CA; Aadi Bioscience Inc; November 2021. Accessed November 2021. 

2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) sirolimus-albumin bound. National Comprehensive Cancer Network, 2021. 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 November 2021. 

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 2.2021. 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 December 2021.

5.FYARRO Prescribing Information. Aadi Bioscience Inc.; November 2021.

6. NCCN Drugs & Biologics Compendium. Sirolimus (albumin-bound), 2025.

7. Wagner AJ, Ravi V, Riedel RF, et al. J Clin Oncol. 2021;39:3669–3680.

8. NCCN Guidelines: Soft Tissue Sarcoma v2.2025.

Codes

Applicable Modifiers

N/A

Policy History