CurrentUnitedHealthcarePolicy CS2026D0077Q

Gamifant (emapalumab‑lzsg) — Medical Benefit Drug Policy (HLH/MAS)

Defines UnitedHealthcare Community Plan medical benefit coverage criteria for Gamifant (emapalumab-lzsg) for primary hemophagocytic lymphohistiocytosis (HLH) and HLH/macrophage activation syndrome (MAS) in Still's disease, and notes state-specific application exceptions.

Policy Summary

PayerUnitedHealthcare

PolicyGamifant (emapalumab-lzsg) coverage for HLH/MAS

Policy CodePolicy CS2026D0077Q

Change TypeApplication section revisedarchived prior version

Effective DateApr 1, 2026

Next Review Date

Key ActionPrior authorization required with submission of medical records confirming diagnostic and prior‑therapy criteria; dosing must follow FDA labeling.

SourceLink

POLICY UPDATE CHANGES

Application section updated to list states where this Medical Benefit Drug Policy does not apply and state-specific guidance.

Archived previous policy version CS2026D0077P referenced in policy history.

6 monthsmax authorization for primary HLH

12 monthsinitial / reauthorization limit for MAS

J9210procedure code

D76.1–D76.3diagnosis codes

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Primary HLH (FDA indication) — Initial therapy

Covered when ALL of the following are met

Primary HLH diagnostic criteria: Submission of medical records confirming EITHER genetic confirmation of a mutation known to cause primary HLH (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2) OR confirmation that five of the eight HLH-2004 diagnostic criteria are present: fever; splenomegaly; cytopenias meeting thresholds (hemoglobin < 9 g/dL OR platelet count < 100 x10^9/L OR neutrophils < 1 x10^9/L); hypertriglyceridemia (fasting triglycerides ≥ 3 mmol/L or ≥ 265 mg/dL) OR hypofibrinogenemia (fibrinogen ≤ 1.5 g/L); hemophagocytosis in bone marrow, spleen, or lymph nodes without malignancy; low or absent NK-cell activity; ferritin ≥ 500 mcg/L; soluble CD25 ≥ 2,400 U/mLgenetic OR 5/8 criteria

HLH-2004 diagnostic framework referenced

Prior treatment requirement: Patient has refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy (examples: etoposide, corticosteroids, cyclosporine, anti-thymocyte globulin, methotrexate)prior therapy failure/intolerance

Step therapy requirement for primary HLH

Concomitant therapy and transplant intent: Gamifant will be administered with dexamethasone; patient is a candidate for hematopoietic stem cell transplant; use is part of induction or maintenance for transplant and will be discontinued at initiation of conditioningtransplant candidate

Authorization limited to no more than 6 months

Administrative and dosing: Provider must not request a planned inpatient admission solely for the purpose of administering Gamifant; dosing must be in accordance with FDA-approved labelingFDA dosing

HLH/MAS in Still's disease (sJIA/AOSD) — Initial therapy

Covered when ALL of the following are met

Diagnosis: Submission of medical records confirming confirmed or suspected systemic juvenile idiopathic arthritis (sJIA) or adult-onset Still's disease (AOSD) with a diagnosis of active macrophage activation syndrome (MAS): ferritin > 684 ng/mL AND at least two of the following laboratory criteria — platelet count ≤ 181 x10^9/L; AST > 48 U/L; triglycerides > 156 mg/dL; fibrinogen ≤ 360 mg/dLferritin and ≥2 lab criteria

Enrollment thresholds from MAS studies

Prior therapy: Patient has had an inadequate response to high-dose intravenous glucocorticoidsprior steroid failure

Step therapy requirement for MAS

Administrative and dosing: Provider must not request a planned inpatient admission solely for administering Gamifant; dosing must follow FDA-approved labeling; initial authorization will be for no more than 12 months

Continuation / Reauthorization criteria

Covered when ALL of the following are met

Clinical response: Documentation of a positive clinical response to Gamifantpositive response

Reauthorization up to 12 months for MAS

Administrative and dosing: Provider must not request a planned inpatient admission solely for the purpose of administering Gamifant; dosing must be in accordance with FDA-approved labelingFDA dosing

Reauthorization will be for no more than 12 months

Gamifant (emapalumab-lzsg) is not proven or medically necessary for the treatment of secondary HLH. Requests for therapy when the diagnosis is secondary HLH should be denied as not medically necessary.

Treatment of secondary HLH with Gamifant is considered not medically necessary. The policy does not support use of Gamifant for secondary HLH diagnoses and such requests will be declined.

Procedure, Diagnosis, and Lab Criteria

Procedure / HCPCSHCPCS

J9210

Injection, emapalumab-lzsg, 1 mg

Diagnosis CodesICD-10

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

inv-08: Ferritin — thresholds

Ferritin threshold (Primary HLH)>= 500 mcg/L

Ferritin threshold (MAS in Still's disease)> 684 ng/mL

Context (HLH diagnostic list)Ferritin ≥ 500 mcg/L is one of the HLH‑2004 diagnostic criteria used to confirm primary HLH

inv-09: Cytopenia thresholds

Hemoglobin< 9 g/dL

Platelet count (HLH)< 100 x10^9/L

Neutrophils< 1 x10^9/L

Platelet count (MAS)≤ 181 x10^9/L

inv-10: Hypertriglyceridemia

Hypertriglyceridemia (HLH diagnostic)>= 265 mg/dL

Alternate units≥ 3 mmol/L

RoleOne of the HLH diagnostic laboratory criteria (hypertriglyceridemia or hypofibrinogenemia)

inv-11: Hypofibrinogenemia

Hypofibrinogenemia (Primary HLH)fibrinogen ≤ 1.5 g/L

Fibrinogen threshold (MAS enrollment criteria)fibrinogen ≤ 360 mg/dL

RoleDefined as one of the HLH lab criteria (or part of MAS lab criteria) for diagnosis/enrollment

What Providers Must Do

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required. Submit medical records (chart notes, laboratory values) confirming diagnostic criteria or genetic mutation for primary HLH, and documentation of prior/refractory therapy as applicable. Dosing must follow the FDA‑approved labeling. Authorizations are time‑limited (initial and reauthorization limits apply).

Submit medical records confirming either a pathogenic gene mutation known to cause primary HLH (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2) OR documentation that at least five of the diagnostic clinical criteria for HLH are present (fever, splenomegaly, specified cytopenias, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, low/absent NK cell activity, ferritin ≥500 mcg/L, soluble CD25 ≥2,400 U/mL).
For primary HLH, provide documentation of refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy (e.g., etoposide, corticosteroids, cyclosporine, anti‑thymocyte globulin, methotrexate).
For HLH/MAS associated with sJIA or AOSD (initial therapy), submit records confirming confirmed or suspected sJIA or AOSD, active MAS with ferritin >684 ng/mL and two of the lab criteria (platelets ≤181 x10^9/L or AST >48 U/L, triglycerides >156 mg/dL, fibrinogen ≤360 mg/dL), and inadequate response to high‑dose IV glucocorticoids.
Gamifant must be administered with dexamethasone and the patient must be a candidate for hematopoietic stem cell transplant when used for primary HLH; therapy is to be discontinued at initiation of conditioning for transplant.
Do not request authorization for a planned inpatient admission solely for Gamifant administration.
Dosing must be consistent with the FDA label. Initial authorizations: up to 6 months for primary HLH; up to 12 months for initial HLH/MAS therapy. Reauthorizations require documentation of positive clinical response and will be for no more than 12 months.
Requests for Gamifant for secondary HLH (not primary HLH or HLH/MAS meeting criteria above) will be denied as not medically necessary.

Step Therapy

Step Therapy / Prior Treatment Requirement

Step‑therapy / prior treatment requirement — For primary HLH, the patient must have refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy. For HLH/MAS (sJIA or AOSD), the patient must have had an inadequate response to high‑dose IV glucocorticoids before Gamifant is authorized.

Documentation Required

Required Medical Records

Required medical records — Submit chart notes and laboratory values confirming either a causative genetic mutation for primary HLH or fulfillment of HLH diagnostic criteria (five of listed clinical features). For HLH/MAS include ferritin and the specified laboratory criteria. Documentation should support diagnosis, prior therapies tried, and clinical course.

Documentation Required

Prior Therapy Documentation

Prior therapy documentation — Provide documentation of inadequate response or intolerance to conventional HLH therapy for primary HLH, or inadequate response to high‑dose IV glucocorticoids for HLH/MAS, including dates, agents used, dosing, and reasons for discontinuation if applicable.

Denial Risk

Documentation & Eligibility Triggers for Denial

Documentation & eligibility triggers for denial — Requests lacking required diagnostic documentation, evidence of prior therapy failure/intolerance when indicated, evidence of FDA‑consistent dosing, or documentation that Gamifant will be discontinued at initiation of transplant conditioning (when applicable) may be denied. Requests for secondary HLH will be denied as not medically necessary.

Denial Risk

Secondary HLH Exclusion

Secondary HLH exclusion — Gamifant is not proven or medically necessary for secondary HLH; such requests will be denied.

Initial Authorization Criteria

Initial therapy — Initial authorization criteria differ by indication

Initial authorization criteria differ by indication

Primary HLH initial: Meets diagnostic criteria (genetic mutation OR 5 of 8 HLH-2004 criteria), has refractory/recurrent/progressive disease or intolerance to conventional HLH therapy, will receive dexamethasone with Gamifant, is a candidate for hematopoietic stem cell transplant with plan to discontinue Gamifant at initiation of conditioning, dosing per FDA labelingas listed

Authorization limited to no more than 6 months

MAS (Still's disease) initial: Confirmed or suspected sJIA/AOSD with active MAS per study thresholds (ferritin > 684 ng/mL and ≥2 of specified labs), inadequate response to high-dose IV glucocorticoids, dosing per FDA labelingas listed

Initial authorization up to 12 months

Step	Requirement
1	Must document prior therapy failure or intolerance: for primary HLH — refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy (examples: etoposide, corticosteroids, cyclosporine, anti‑thymocyte globulin, methotrexate); for HLH/MAS in Still's disease — inadequate response to high‑dose intravenous glucocorticoids.

Definitions

inv-19: Primary hemophagocytic lymphohistiocytosis (HLH)

DefinitionA genetic/immunologic hyperinflammatory syndrome characterized by immune dysregulation, hemophagocytosis, and high mortality

Typical presentationOften presents in infancy; may include fever, splenomegaly, cytopenias, and elevated ferritin

Diagnostic frameworkDiagnosis per HLH‑2004 criteria (genetic confirmation or 5 of 8 clinical/laboratory criteria)

Treatment contextEmapalumab studied to control disease and enable hematopoietic stem cell transplantation

inv-20: Macrophage activation syndrome (MAS)

DefinitionA form of HLH that occurs as a severe complication of rheumatic diseases, most often in Still's disease (sJIA/AOSD)

Diagnostic featuresCharacterized by hyperferritinemia and laboratory abnormalities (e.g., thrombocytopenia, elevated AST, hypertriglyceridemia, low fibrinogen)

Relation to Still's diseaseOccurs in patients with confirmed or suspected sJIA or AOSD and has been the indication for emapalumab trials when refractory to high‑dose glucocorticoids

OpenPayer

Gamifant (emapalumab‑lzsg) — Medical Benefit Drug Policy (HLH/MAS)

Coverage Criteria for Gamifant (emapalumab-lzsg)

Procedure, Diagnosis, and Lab Criteria

What Providers Must Do

Initial Authorization Criteria

Reauthorization and Continuation

Step Therapy Requirements

Site of Care Requirements

Background

Definitions

Revision History