U.S. Food and Drug Administration (FDA)-Approved Indications

Sirolimus protein-bound particles for injectable suspension albumin-bound is available as Fyarro (Aadi Bioscience, Inc.) and contains the active ingredient, sirolimus, formulated as albumin-bound nanoparticles. Sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, formerly mammalian target of rapamycin) inhibitor. mTOR is involved downstream of the PI3K/AKT pathway and controls important cellular processes (i.e., cell survival, growth, and proliferation) and is frequently dysregulated in several human cancers (Aadi Bioscience, 2021).

According to the prescribing information, the use of Fyarro is contraindicated in individuals with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

Per the prescribing information, sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro) is contraindicated for individuals with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

Per the prescribing information, sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro) carries the following warnings and precautions:

The most common (≥30%) adverse reactions include stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia. The most common (≥6%) grade 3 to 4 laboratory abnormalities include decreased lymphocytes, increased glucose, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase (Aadi Bioscience, 2021).

Refer to full prescribing information for Fyarro for drug interactions and use in specific populations.

On November 22, 2021, the U.S. Food and Drug Administration (FDA) approved Fyarro (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). The FDA granted priority review, fast track designation, breakthrough therapy designation, and orphan drug designation for Fyarro. The FDA approval was based on supporting data from the AMPECT study (FDA, 2021).

Wagner and colleagues (2021) evaluated the efficacy and safety of Fyarro (sirolimus protein-bound particles for injectable suspension) (albumin-bound) in the AMPECT study, a phase 2, multicenter, single-arm clinical trial consisting of 34 adult participants (31 participants evaluable for efficacy and 34 participants evaluable for safety) with locally advanced unresectable or metastatic malignant PEComa. Participants received Fyarro 100 mg/m

intravenously once weekly for 2 weeks in 3-week cycles until disease progression or unacceptable toxicity. The primary outcome was objective response rate and secondary outcomes included duration of response, progression-free survival, and safety. The results included the overall response rate as 39% (12 of 31; 95% Confidence Interval [CI], 22 to 58) with one complete and 11 partial responses, 52% (16 of 31) of participants had stable disease, 10% (3 of 31) had progressive disease. Responses were of rapid onset (67% by week 6) and durable. Median duration of response was not achieved after a median follow-up for response of 2.5 years, with 7 of 12 responders with treatment ongoing (range, 5.6-47.2+ months). The median progression-free survival was 10.6 months (95% CI, 5.5 months to not reached), and the median overall survival was 40.8 months (95% CI, 22.2 months to not reached). Treatment-related adverse effects were mainly grade 1 or 2 and manageable for long-term treatment. There was an absence of ≥ grade 4 treatment-related events. The results supported the conclusion of Fyarro as a new and viable treatment option for individuals with malignant PEComa.

: Requires Precertification:

Precertification of sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro) is required of all Aetna participating providers and members in applicable plan designs. For precertification of sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro), call (866) 752-7021 (Commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

Perivascular Epithelioid Cell Tumor (PEComa)

Aetna considers sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro) medically necessary for the treatment of locally advanced unresectable or metastatic malignant PEComa when used as a single agent.

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of sirolimus protein-bound particles for injectable suspension albumin-bound (Fyarro) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Sirolimus protein-bound particles for injectable suspension albumin-bound is supplied as Fyarro lyophilzed powder containing 100 mg of sirolimus formulated as albumin-bound particles in single-dose vial for reconstitution for intravenous (IV) infusion.

Perivascular Epithelioid Cell Tumor

The recommended dosage is 100 mg/m

administered as an IV infusion over 30 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Refer to full prescribing information for Fyarro for preparation and administration instructions and dosage modifications.

Source: Aadi Bioscience, 2021