CurrentUnitedHealthcarePolicy IEXD0077.08

Gamifant (emapalumab-lzsg) — Coverage Criteria

Defines medical necessity criteria and prior authorization requirements for Gamifant (emapalumab-lzsg) under UnitedHealthcare Individual Exchange medical benefit plans (excluding MA, NV, NY). Applies to providers requesting coverage for treatment of primary HLH and HLH/MAS in Still's disease.

Policy Summary

PayerUnitedHealthcare

PolicyGamifant (emapalumab-lzsg) — Coverage Criteria

Policy CodePolicy IEXD0077.08

Change TypeRevised coverage criteria (operational)

Effective DateJan 1, 2026

Next Review Date

Key ActionSubmit prior authorization with medical records confirming diagnostic criteria and treatment intent; dosing must follow FDA labeling.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria; added criterion requiring the provider does not request a planned inpatient admission for the sole purpose of administering Gamifant.

6 monthsMax initial auth (primary HLH)

12 monthsInitial/reauth (HLH/MAS)

J9210HCPCS

Excludes MA,NV,NYGeographic applicability

53.8%–64.7%

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Coverage and Medical Necessity Criteria

Medical necessity criteria

Covered when ALL of the following are met for primary HLH:

Primary HLH coverage criteria: 1) Submission of medical records confirming either a causative gene mutation (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2) OR fulfillment of five HLH diagnostic criteria (fever; splenomegaly; two cytopenias: hemoglobin <9 g/dL OR platelet count <100 x10^9/L OR neutrophils <1 x10^9/L; one of: fasting triglycerides ≥265 mg/dL OR fibrinogen ≤1.5 g/L; hemophagocytosis in bone marrow/spleen/lymph nodes without malignancy; low/absent NK‑cell activity; ferritin ≥500 mcg/L; soluble CD25 ≥2,400 U/mL). 2) Patient has refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. 3) Gamifant is being used as part of the induction or maintenance phase of hematopoietic stem cell transplant and will be discontinued at initiation of conditioning. 4) Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant. 5) Dosing is in accordance with FDA‑approved labeling. 6) Authorization limited to no more than 6 months.

Preserves requirement for HSCT candidacy and coordination with transplant

HLH/MAS in Still's disease (sJIA/AOSD) initial therapy: 1) Submission of medical records confirming confirmed or suspected sJIA or AOSD and diagnosis of active MAS with ferritin >684 ng/mL and at least two of the following: platelet count ≤181 x10^9/L; AST >48 U/L; triglycerides >156 mg/dL; fibrinogen ≤360 mg/dL. 2) Inadequate response to high‑dose IV glucocorticoids. 3) Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant. 4) Dosing per FDA labeling. 5) Initial authorization up to 12 months.

Applies to induction/initial use in MAS related to Still's disease

Continuation/Reauthorization for HLH/MAS: 1) Documentation of positive clinical response to Gamifant. 2) Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant. 3) Dosing per FDA labeling. 4) Reauthorization limited to no more than 12 months.

Continuation criteria for ongoing therapy

Gamifant (emapalumab‑lzsg) is not indicated for secondary hemophagocytic lymphohistiocytosis (HLH) under this policy. The clinical evidence and policy language state that Gamifant is not proven or medically necessary for the treatment of secondary HLH.

Use of Gamifant for secondary HLH is considered not medically necessary. Requests for coverage for secondary HLH will be declined consistent with the policy statement that Gamifant is not proven to be effective in this population.

Applicable Codes and Key Clinical Thresholds

Applicable HCPCS/Drug codeHCPCS

J9210

Injection, emapalumab-lzsg, 1 mg.

Relevant diagnosis codesICD-10

D76.1	Hemophagocytic lymphohistiocytosis.
D76.2	Hemophagocytic syndrome, infection-associated.
D76.3	Other histiocytosis syndromes.

inv-06: Ferritin threshold for MAS

Ferritin thresholdFerritin > 684 ng/mL

ContextRequired for diagnosis of active MAS in sJIA/AOSD for initial therapy

Supporting lab ruleMust be accompanied by at least two of: platelets ≤181 x10^9/L; AST >48 U/L; triglycerides >156 mg/dL; fibrinogen ≤360 mg/dL

Prior Authorization, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization is required for Gamifant (emapalumab) prior to initiation. Submit clinical documentation (chart notes, lab results, genetic testing, prior therapy records) to support diagnosis and indication. Authorizations: for primary HLH, up to 6 months; for sJIA/AOSD-associated MAS, initial authorization up to 12 months; continuations/reauthorizations up to 12 months when criteria met.

Prior authorization required before drug administration
Include medical records, laboratory values, and genetic testing when applicable
Authorization length: primary HLH — ≤ 6 months; MAS (sJIA/AOSD) initial ≤ 12 months; reauthorization ≤ 12 months

Step Therapy

Prior Therapy Requirements

Gamifant is approved only when prior/concurrent therapy requirements are met. For primary HLH, document refractory, recurrent, progressive disease or intolerance to conventional HLH therapy (e.g., etoposide, corticosteroids, cyclosporine, anti‑thymocyte globulin, methotrexate) and candidate for hematopoietic stem cell transplant. For MAS in sJIA/AOSD, document inadequate response to high‑dose IV glucocorticoids prior to initiating Gamifant. Provide medical records confirming prior therapies and clinical response.

Clinical Background

Primary hemophagocytic lymphohistiocytosis (HLH) is a rare, severe hyperinflammatory syndrome; macrophage activation syndrome (MAS) is a related, life‑threatening form of HLH that can occur in Still's disease. Emapalumab (Gamifant) is a targeted anti‑interferon‑gamma therapy used in specified primary HLH and MAS scenarios, but policy limits its use and requires documentation of clinical response for continuation. For continuation of therapy the policy requires demonstration of a positive clinical response, adherence to FDA dosing, and specifies that reauthorization will be for no more than 12 months; the policy also reiterates that Gamifant is not proven or medically necessary for secondary HLH.

Key Definitions

inv-12: Primary HLH definition / key points

DefinitionPrimary hemophagocytic lymphohistiocytosis (HLH) — a rare, often infant‑onset hyperinflammatory syndrome characterized by immune dysregulation and high mortality; indicated population for Gamifant is patients with refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy

Diagnostic pathwaysDiagnosis supported by either a causative gene mutation (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2) OR fulfillment of five HLH diagnostic criteria including fever, splenomegaly, cytopenias, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, low/absent NK‑cell activity, ferritin ≥500 mcg/L, or soluble CD25 ≥2400 U/mL

Treatment linkageGamifant is indicated for primary HLH as part of induction/bridging for patients who are HSCT candidates; dosing per FDA labeling and authorization limited to up to 6 months

inv-13: MAS definition in Still's disease

DefinitionMacrophage activation syndrome (MAS) in Still's disease (sJIA/AOSD) — a severe form of HLH occurring in Still's disease characterized by hyperferritinemia and cytopenias