CurrentHealth NetPolicy CP PHAR.574

Sirolimus Protein‑Bound Particles (Fyarro), Topical Gel (Hyftor)

Coverage and clinical criteria for sirolimus protein-bound particles (Fyarro) for PEComa and topical sirolimus gel (Hyftor) for facial angiofibroma associated with tuberous sclerosis; applies to Health Net lines of business included under the policy.

Policy Summary

PayerHealth Net

PolicySirolimus Protein‑Bound Particles (Fyarro), Topical Gel (Hyftor)

Policy CodePolicy CP PHAR.574

Change TypeNo material change

Effective DateMar 1, 2022

Next Review Date

Key ActionPrior authorization is required; submit documentation showing the member meets the listed initial approval criteria for Fyarro or Hyftor.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

100Fyarro max dose mg/m2

6 moCommercial initial duration

12 moMedicaid/HIM continued duration

≥6Hyftor minimum age

J9331HCPCS cited

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Initial Therapy — Fyarro for PEComa

Initial Approval Criteria — Fyarro for PEComa (must meet all):

ALL of the following

Diagnosis of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
Request is for Fyarro (sirolimus protein-bound particles).
Prescribed by or in consultation with an oncologist.
Age ≥ 18 years.
Member does not have PEComa type lymphangioleiomyomatosis.
Use as a single agent.
Dose limits
- Dose does not exceed 100 mg/m² IV on Days 1 and 8 of each 21-day cycle; administered as an IV infusion over approximately 30 minutes.
- Dose is supported by practice guidelines or peer-reviewed literature for the prescribed regimen (prescriber must submit supporting evidence).
Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — Hyftor for Facial Angiofibroma (Tuberous Sclerosis)

Initial Approval Criteria — Hyftor for Facial Angiofibroma associated with Tuberous Sclerosis (must meet all):

ALL of the following

Diagnosis of facial angiofibroma associated with tuberous sclerosis.
Request is for Hyftor (sirolimus topical gel).
Prescribed by or in consultation with an oncologist, neurologist, or dermatologist.
Age > 6 years.
Maximum dose by age
- Age 6 to 11 years: maximum 600 mg (approx. 2 cm tube equivalent) per application area as specified in dosing guidance.

Continued Therapy — Fyarro and Hyftor

Continuation Therapy — Fyarro and Hyftor (must meet all applicable criteria):

ALL of the following

Member is currently receiving the requested medication via the Centene benefit, or documentation supports that the member is currently receiving the medication and has received it for at least 30 days.
Continued therapy specifics for Fyarro (PEComa)
- ALL of the following
  - Request is for Fyarro.
  - Member is responding positively to therapy (clinical evidence of benefit).
  - If request is for a dose increase, the new dose must meet one of the following:

Coding and Dosing Information

Referenced HCPCS CodesHCPCS

J9331

Injection, sirolimus protein-bound particles (Fyarro) 1 mg

Fyarro dosing maximum — 100 mg/m2 IV on Days 1 and 8 of each 21-day cycle

Maximum dose100 mg/m2 IV administered on Days 1 and 8 of each 21-day cycle

AdministrationIV infusion over 30 minutes per dose

Indication contextDosing specified for Fyarro in treatment of locally advanced unresectable or metastatic malignant PEComa

Hyftor pediatric maximums — per-age dosing (600 mg / 800 mg by formulation length)

Age 6–11 yearsMaximum 600 mg (2 cm) per dosing guidance

Age ≥12 yearsMaximum 800 mg (2.5 cm) per dosing guidance

AdministrationApply to affected facial skin twice daily (topical gel)

Commercial continued therapy duration for PEComa — 6 months or to the member's renewal date

Commercial continued therapy duration6 months or to the member's renewal date, whichever is longer

Medicaid/HIM continued therapy duration12 months (per policy)

ContextApplies to continued therapy for PEComa when continuation criteria are met

Provider Requirements and Billing Notes

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for Fyarro (sirolimus protein‑bound particles) or Hyftor. Requests for sirolimus (HCPCS J9331) are informationally referenced here — providers must follow the Health Net prior authorization process and submit PA requests that meet the clinical criteria in this policy.

Prior authorization required for Fyarro and Hyftor
HCPCS J9331 is referenced for sirolimus (informational)

Documentation Required

Required Documentation

Providers must submit supporting clinical documentation with the prior authorization request. Acceptable documentation includes office/clinic chart notes, relevant laboratory results, pathology reports, imaging, and consultation notes that substantiate the diagnosis, prior treatments, dosing rationale, and clinical response.

Include office chart notes and relevant labs
Include diagnostic reports, imaging, and consultation notes as applicable
Document prior therapies and clinical rationale for requested agent

Note

Formulary / Off‑Label Routing

When the requested use is off‑label or the drug is not on the member’s formulary/PDL, route the request per the applicable formulary or off‑label policies for the member’s line of business. For commercial and marketplace members follow CP.CPA.190 (commercial) or HIM.PA.33 (marketplace) as applicable; for Medicaid follow CP.PMN.255 / CP.PMN.16 / CP.PMN.53 per the policy references below.

If drug is on formulary/PDL: follow the relevant line of business formulary policy (e.g., CP.CPA.190)
If drug is non‑formulary: follow the non‑formulary policy for the line of business (e.g., HIM.PA.103 for marketplace, CP.PMN.16 for Medicaid)
For off‑label uses not addressed in this policy: follow off‑label use policies (e.g., CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid)

Denial Risk

Non‑FDA Indications

Requests for non‑FDA indications that are not specifically addressed by this policy may be denied unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies and any evidence of coverage documents. Provide peer‑reviewed literature, practice guideline support, or other compelling clinical evidence when seeking coverage for non‑FDA uses.

Non‑FDA indications require robust supporting evidence per off‑label policies
Cite practice guidelines or peer‑reviewed literature when available

Billing Rule

Coding Guidance and Code Inclusion

Codes listed in this policy (e.g., HCPCS J9331 for sirolimus protein‑bound particles) are provided for informational purposes only. Inclusion of a code does not guarantee coverage. Providers should reference the most up‑to‑date professional coding guidance when preparing and submitting claims.

HCPCS J9331 referenced for sirolimus (Fyarro) — informational only
Verify current coding rules and payer-specific billing instructions prior to claim submission

Background and Drug Information

Fyarro (sirolimus protein‑bound particles) and Hyftor (topical sirolimus gel) are members of the mTOR inhibitor drug class. Fyarro is FDA‑approved for adult patients with locally advanced unresectable or metastatic malignant PEComa and is administered intravenously; dosing guidance in the prescribing information limits administration to 100 mg/m2 IV on Days 1 and 8 of each 21‑day cycle, unless a dose is supported by practice guidelines or peer‑reviewed literature. Hyftor is FDA‑approved for treatment of facial angiofibroma associated with tuberous sclerosis in patients aged 6 years and older as a topical sirolimus formulation (see Hyftor prescribing information for full dosing and administration details).

Definitions

PEComa — perivascular epithelioid cell tumor definition

TermPerivascular epithelioid cell tumor (PEComa)

AbbreviationPEComa = perivascular epithelioid cell tumor

UsageReferenced as the indication for which Fyarro is indicated (locally advanced unresectable or metastatic malignant PEComa)

Fyarro — sirolimus protein-bound particles definition / product name

Product nameFyarro (sirolimus protein-bound particles)

FormulationSirolimus protein-bound particles for IV administration

Indication noteFDA-approved for adult patients with locally advanced unresectable or metastatic malignant PEComa

Hyftor — topical sirolimus gel (prescribing information reference)

Product nameHyftor (topical sirolimus gel)

SourcePrescribing information referenced (Hyftor Prescribing Information, March 2022)

Indication noteFDA-approved for facial angiofibroma associated with tuberous sclerosis in patients age ≥ 6 years

Initial Authorization Criteria

Initial therapy rules 6 consolidated initial authorization logic for products

Use the product-specific initial criteria below to determine authorization for the requested sirolimus product

Fyarro initial: 1) Diagnosis of locally advanced unresectable or metastatic malignant PEComa; 2) Request is for Fyarro; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) Member does not have PEComa-type lymphangioleiomyomatosis; 6) Use as a single agent; 7) Dose does not exceed 100 mg/m2 IV on Days 1 and 8 of each 21-day cycle OR dose is supported by practice guidelines/peer-reviewed literature. Prescribed regimen must be FDA-approved or recommended by NCCN; Approval duration: 6 months.

Hyftor initial: 1) Diagnosis of facial angiofibroma associated with tuberous sclerosis; 2) Request is for Hyftor; 3) Prescribed by or in consultation with an oncologist, neurologist, or dermatologist; 4) Age >= 6 years; 5) Dose does not exceed pediatric maxima: ages 6-11 = 600 mg (2 cm); age >=12 = 800 mg (2.5 cm).

Continuation/ Renewal Criteria

inv-23: Fyarro continuation 6 criteria for continued therapy

Covered for continuation when ALL of the following are met

Fyarro continued therapy criteria: 1) Member currently receiving Fyarro via Centene benefit with documentation of receipt for at least 30 days; 2) Member is demonstrating a positive clinical response to therapy; 3) Dose increase requests must either not exceed 100 mg/m2 IV on Days 1 and 8 of each 21-day cycle or be supported by practice guidelines/peer-reviewed literature with submitted evidence; Prescribed regimen must be FDA-approved or recommended by NCCN.

inv-24: Hyftor continuation 6 criteria for continued topical therapy

Covered for continuation when ALL of the following are met

Hyftor continued topical therapy criteria: 1) Member currently receiving Hyftor via Centene benefit or has previously met initial approval criteria; 2) Member is demonstrating a positive clinical response to therapy as evidenced by reduction in size and/or redness of facial angiofibroma; 3) Continuity of care provisions apply where state and product regulations require (refer to state addendums).

inv-25: PEComa continued therapy duration (commercial)

Commercial continuation duration update (PEComa)

PEComa commercial duration: Commercial continued therapy duration has been updated to 6 months or to the member's renewal date, whichever is longer.

Step Therapy / Formulary Routing

Step	Action / Routing
If the drug is on the formulary (commercial, health insurance marketplace) or on the PDL (Medicaid)	Follow the applicable no‑coverage criteria policy for the line of business (commercial: CP.CPA.190; health insurance marketplace: HIM.PA.33; Medicaid: CP.PMN.255)
If the drug is NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid)	Refer to the non‑formulary policy for the relevant line of business (commercial: CP.CPA.190; health insurance marketplace: HIM.PA.103; Medicaid: CP.PMN.16)
If the drug has undergone a recent label change (within the last 6 months) not yet reflected in this policy	Refer to the specified routing above (formulary/non‑formulary) as applicable or follow off‑label use policy when the requested use is not listed under exclusions (off‑label policies: commercial CP.CPA.09; health insurance marketplace HIM.PA.154; Medicaid CP.PMN.53)
If the requested use (diagnosis, age, dosing regimen) is not specifically listed under the policy's exclusions and formulary routing does not apply	Refer the request to the off‑label use policy for the relevant line of business (commercial: CP.CPA.09; health insurance marketplace: HIM.PA.154; Medicaid: CP.PMN.53)

Policy Revision History

2025-02-25policy_review/approvalLatest

1Q 2025 annual review: updated PEComa continued therapy commercial duration to 6 months or to the member's renewal date; references reviewed and updated; P&T approval recorded.

2023-11-13annual_review

1Q 2024 annual review: no significant clinical changes; references reviewed and updated.

2022-11-03annual_review

1Q 2023 annual review: no significant clinical changes; references reviewed and updated; P&T approval documented.

2022-09-19template_change

Template changes applied to other diagnoses/indications and continued therapy section.

2022-06-30policy_update

RT4: added Hyftor to policy (date noted) and associated updates recorded.

2022-04-14policy_update

RT4: added Hyftor to policy (initial addition recorded).

2021-12-14policy_creation

Policy created (initial creation date recorded).

OpenPayer

Sirolimus Protein‑Bound Particles (Fyarro), Topical Gel (Hyftor)

Coverage and Medical Necessity Criteria

Coding and Dosing Information

Provider Requirements and Billing Notes

Background and Drug Information

Definitions

Initial Authorization Criteria

Continuation/ Renewal Criteria

Step Therapy / Formulary Routing

Quantity Limits

Policy Revision History