Sirolimus Protein-Bound Particles (Fyarro) and Topical Sirolimus Gel (Hyftor)
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This policy defines medical necessity and prior authorization criteria for Fyarro (IV sirolimus protein-bound particles) for PEComa and Hyftor (topical sirolimus gel) for facial angiofibroma in tuberous sclerosis, and describes approval durations and dosing limits for affected members under Ambetter Georgia lines of business.
No material clinical or coverage changes in this revision.
Coverage Criteria
Initial Therapy — PEComa (Fyarro)
Covered when ALL of the following are met:
Initial Therapy — Facial Angiofibroma (Hyftor)
Covered when ALL of the following are met:
Continued Therapy — PEComa (Fyarro)
Covered when ALL of the following are met:
Continued Therapy — Facial Angiofibroma (Hyftor)
Covered when ALL of the following are met:
Other/Off-label Uses
Considerations when requested use is not listed:
Notable coverage criteria snippets
Policy includes specific authorization durations and lesion criteria for topical use in facial angiofibromas and for PEComa continued therapy.
Referenced in facial angiofibroma initial criteria and revision notes
Stated in policy revision entries (1Q 2025 and Medicaid/HIM revisions).
Requests for uses that are not FDA‑approved and not specifically addressed in this policy are excluded unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policy. For Commercial members, reference CP.CPA.09; for Health Insurance Marketplace members, reference HIM.PA.154; and for Medicaid members, reference CP.PMN.53. Absent that documentation or an evidence of coverage allowance, the requested non‑FDA indication will not be authorized.
When there is a conflict between this clinical policy and any state Medicaid coverage provisions, the state Medicaid provisions take precedence. Providers should consult the applicable state Medicaid manual for specific coverage rules and follow those provisions for Medicaid members.
If the requested indication is off‑label or not listed in Section III, prior authorization may still be considered only when the request is supported by sufficient clinical documentation per the applicable off‑label use policy. Follow the referenced off‑label policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) and submit supporting evidence of safety and efficacy; without such documentation the service is considered not authorized.
Coding and Dosing
| 100 mg/m² | Fyarro IV dose on Days 1 and 8 of each 21-day cycle |
| Topical gel 0.2% | Hyftor formulation: 2 mg sirolimus per gram |
| 600 mg (2 cm) | Hyftor dosing for ages 6–11 |
| 800 mg (2.5 cm) | Hyftor dosing for age ≥12 |
| J9331 | Injection, sirolimus protein-bound particles (Fyarro), 1 mg |
Provider Actions and Billing Notes
Prior authorization required
Prior authorization is required for requests for Fyarro or Hyftor; requests must meet the listed diagnosis, prescriber type, age, dosing, and other criteria in the policy before authorization will be granted.
Prior authorization for Fyarro (J9331)
When requesting authorization or submitting claims for Fyarro, reference HCPCS J9331 (Injection, sirolimus protein‑bound particles, 1 mg) and follow the plan's prior authorization procedures; the policy indicates prior authorization is implied for Fyarro and providers should reference coding when requesting authorization.
Formulary / off‑label routing required
If the requested use is not listed in the policy, route the request per the formulary/non‑formulary and off‑label use policies referenced for the member's line of business rather than assuming automatic coverage under this policy.
- Follow CP.CPA.190, HIM.PA.33, CP.PMN.255 for no‑coverage routing when drug is on formulary/PDL.
- Follow CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary routing when drug is not on formulary/PDL.
- Refer to off‑label use policies CP.CPA.09, HIM.PA.154, CP.PMN.53 when the indication/age/dosing is not listed.
Revisions: continued therapy durations updated (PEComa)
Policy revision notes indicate changes to continued‑therapy approval durations for PEComa (commercial updated to 6 months or to the member's renewal date; Medicaid/HIM initial approval revised to 12 months). Providers should account for these duration differences when requesting continued authorization.
Submit clinical documentation to support authorization
Providers must submit supporting clinical documentation (e.g., office chart notes, lab results, or other clinical information) demonstrating the member meets all approval criteria when requesting authorization.
Follow policy and plan contractual terms; no payment guarantee
This policy is a guide to medical necessity and does not guarantee payment; providers must follow the clinical policy and the member's benefit documents and contractual terms when submitting requests or claims.
Risk of denial for non‑covered (non‑FDA) indications
Requests for non‑FDA approved indications that are not addressed in this policy may be denied unless sufficient documentation of efficacy and safety is provided per the off‑label use policies referenced in the document.
Coding and code‑related denial risk
Claims and authorization requests may be denied if submitted with incorrect or inappropriate coding; the policy notes that codes listed are informational and inclusion or exclusion of codes does not guarantee coverage.
- HCPCS code J9331 is listed for Fyarro; verify coding prior to claim submission.
- Inclusion or exclusion of codes in the policy is informational only and does not ensure payment.
Initial Therapy Criteria
Initial therapy rules
Initial coverage criteria for each FDA‑approved indication:
Initial therapy notes
Initial approval duration notes and revision highlights:
From policy revision entries.
Continuation / Continued Therapy Criteria
Continuation therapy rules
Continuation criteria for members already receiving therapy:
PEComa continued therapy durations
Continued therapy durations updated for PEComa (as noted in policy revisions):
Updated in 1Q 2025 annual review entries.
Referenced in policy revision notes.
Step Therapy
| When requested indication is not listed | Routing instruction |
|---|---|
| Drug recently had label change within last 6 months (e.g., new indication, age expansion, new dosing) not yet reflected in this policy | Refer to formulary/no‑coverage or non‑formulary policy for the applicable line of business (CP.CPA.190, HIM.PA.33, CP.PMN.255 for on‑formulary; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary) |
| Requested use not listed in Section III and criterion 1 does not apply | Refer to the off‑label use policy for the applicable line of business (CP.CPA.09 for commercial; HIM.PA.154 for Health Insurance Marketplace; CP.PMN.53 for Medicaid) |
| Step therapy sequence provided? | Notes |
|---|---|
| No specific step therapy sequence provided in this policy excerpt | Policy revisions reference continued‑therapy duration changes and criteria but do not define step edits or ordering |
Quantity Limits and Dosing
Site of Care
Site of care — infusion center or home (topical)
Fyarro is administered as an IV infusion over 30 minutes (infusion center setting); Hyftor is applied topically and may be used at home per the dosing instructions.
- Fyarro: IV infusion over 30 minutes on Days 1 and 8 of each 21‑day cycle
- Hyftor: apply to affected facial skin twice daily (topical, home application)
Infusion center billing — HCPCS J9331 for Fyarro
When billing for Fyarro administered in an infusion setting, use HCPCS code J9331 (Injection, sirolimus protein‑bound particles, 1 mg) and follow professional coding guidance; inclusion of the code in this policy does not guarantee coverage.
Background
Sirolimus in this policy refers to two different formulations: Fyarro (sirolimus protein‑bound particles for injection) and a topical sirolimus gel (Hyftor). Coverage rules in this document apply to the FDA‑approved indications for these products; non‑addressed uses require off‑label documentation per the referenced policies. For Medicaid members, state Medicaid coverage rules override conflicting provisions in this clinical policy, so providers must verify state guidance when treating Medicaid enrollees.
Definitions
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