CurrentColorado Rocky Mountain Health PlansPolicy CS2026D0077Q

Gamifant (Emapalumab-Lzsg) medical benefit drug policy

Defines coverage criteria, initial and continuation authorization limits, applicable diagnosis and HCPCS codes, and state application notes for Gamifant (emapalumab-lzsg) for treatment of primary HLH and HLH/MAS in Still's disease (sJIA/AOSD). Applies to UnitedHealthcare Community Plan medical benefit drug coverage, with specific state exceptions.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyGamifant (Emapalumab-Lzsg) medical benefit drug policy

Policy CodePolicy CS2026D0077Q

Change TypeApplication/state applicability updates; archived prior versions

Effective DateApr 1, 2026

Next Review Date

Key ActionSubmit medical records confirming genetic mutation OR five diagnostic criteria for primary HLH, or required labs/diagnosis and inadequate steroid response for HLH/MAS; dosing must follow FDA label; initial and reauthorization durations limited (6 months for primary HLH, 12 months for MAS).

POLICY UPDATE CHANGES

Removed content/language pertaining to Indiana and Louisiana and removed language indicating the policy did not apply to Indiana; archived previous policy versions CS2026D0077P and CSIND0077.07.

Effective date set to April 1, 2026 for this policy version.

2Indications with approved criteria

6Max initial auth months (primary HLH)

12Max initial/reauth months (MAS)

Coverage Summary

Emapalumab (Gamifant) is an IFNγ-neutralizing monoclonal antibody indicated for primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance to conventional therapy, and for HLH/macrophage activation syndrome (MAS) in known or suspected Still's disease (including sJIA/AOSD) with inadequate response or intolerance to glucocorticoids. In clinical studies of primary HLH (NI-0501-04), 64.7% overall response at end of treatment and an 88.2% response at any time were observed, with a median time to first response of 8 days; many patients were able to proceed to hematopoietic stem cell transplantation (about 65% underwent HSCT with engraftment rates of 86.4%). In pooled HLH/MAS studies, a complete response rate of 53.8% (95% CI: 37.2, 69.9) was reported. Major adverse events observed across studies included infections (bacterial, fungal, viral, including CMV), and infusion-related reactions, along with other events such as hypertension and pyrexia; serious and fatal events were reported largely consistent with HLH complications.

Coverage Rationale - Primary HLH

Gamifant is proven and medically necessary for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in patients who meet ALL of the following criteria:

ALL of the following

Confirmation of primary HLH
- Gene mutation option: Confirmation of a gene mutation known to cause primary HLH (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2)
- HLH-2004 diagnostic criteria option: Confirmation that five of the following clinical characteristics are present: Fever; Splenomegaly; Two cytopenias in peripheral blood (Hemoglobin < 9 g/dL OR Platelet count < 100 x 10^9/L OR Neutrophils < 1 x 10^9/L); One of: Hypertriglyceridemia defined as fasting triglycerides ≥ 3 mmol/L or ≥ 265 mg/dL OR Hypofibrinogenemia defined as fibrinogen ≤ 1.5 g/L; Hemophagocytosis in bone marrow, spleen, or lymph nodes with no evidence of malignancy; Low or absent natural killer cell activity; Ferritin ≥ 500 mcg/L; Soluble CD25 (soluble IL-2 receptor) ≥ 2,400 U/mL5 of 8
Refractory or intolerant to conventional therapy: Patient has refractory, recurrent or progressive disease or intolerance with conventional HLH therapy (e.g., etoposide, corticosteroids, cyclosporine, anti-thymocyte globulin, methotrexate)
Coadministration: Gamifant will be administered with dexamethasone
HSCT candidacy: Patient is a candidate for hematopoietic stem cell transplant
Use relative to HSCT conditioning: Gamifant is being used as part of the induction or maintenance phase of hematopoietic stem cell transplant, which is to be discontinued at the initiation of conditioning for stem cell transplant
Inpatient admission restriction: Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant
Planned inpatient admission solely for administration is a denial risk
Dosing is in accordance with the United States Food and Drug Administration approved labeling
Authorization duration: Authorization will be for no more than 6 months6 months

Coverage Rationale - HLH/MAS in Still's disease (sJIA/AOSD)

Gamifant is medically necessary for the treatment of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in patients who meet ALL of the following criteria:

ALL of the following

sJIA/AOSD documentation: Submission of medical records (e.g., chart notes, laboratory values) confirming confirmed or suspected diagnosis of systemic juvenile idiopathic arthritis (sJIA) or adult onset Still's disease (AOSD)
Active MAS diagnosis: Diagnosis of active MAS with both of the following: Ferritin > 684 ng/mL AND Two of the following laboratory criteria: Platelet count ≤ 181 x 10^9/L; AST > 48 U/L; Triglycerides > 156 mg/dL; Fibrinogen level ≤ 360 mg/dLFerritin > 684 ng/mL + any 2 lab criteria
Both ferritin threshold AND any two lab criteria required
Inadequate steroid response: Patient has had an inadequate response to high-dose intravenous glucocorticoids

Continuation / Reauthorization Criteria

Continuation of Therapy - HLH/MAS

Reauthorization criteria for continued coverage:

ALL of the following

Clinical response: Documentation of a positive clinical response to Gamifant
Inpatient admission restriction: Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant
Dosing is in accordance with the FDA approved labeling
Reauthorization duration: Reauthorization will be for no more than 12 months12 months

Not Medically Necessary / Exclusions

Not Medically Necessary

Exclusion statement in policy:

ALL of the following

Not medically necessary for secondary HLH: Gamifant is not proven or medically necessary for the treatment of secondary HLH

Provider Actions / Prior Authorization Requirements

Prior Authorization

Authorization required with documentation

Submit medical records (chart notes, laboratory values) confirming either a genetic mutation known to cause primary HLH OR fulfillment of five HLH diagnostic criteria; for HLH/MAS, submit required labs/diagnosis plus documentation of inadequate response to high‑dose IV glucocorticoids. Dosing must follow the FDA‑approved labeling. Initial authorization durations are limited to no more than 6 months for primary HLH and no more than 12 months for HLH/MAS; reauthorization limited to durations consistent with the policy. Include HCPCS code J9210 on requests for emapalumab (Gamifant).

Documentation Required

Required diagnostic and response documentation

Provide genetic testing results demonstrating a pathogenic mutation known to cause primary HLH OR documentation that the patient meets five HLH diagnostic criteria (e.g., fever, splenomegaly, two cytopenias with thresholds: hemoglobin < 9 g/dL, platelets < 100 x 10^9/L, or neutrophils < 1 x 10^9/L; fasting triglycerides ≥ 3 mmol/L or ≥ 265 mg/dL OR fibrinogen ≤ 1.5 g/L; hemophagocytosis; low/absent NK activity; ferritin ≥ 500 mcg/L; soluble CD25 ≥ 2,400 U/mL). For HLH/MAS in Still's disease, provide documentation of confirmed or suspected sJIA/AOSD, ferritin > 684 ng/mL AND two of the specified laboratory criteria (platelets ≤ 181 x 10^9/L; AST > 48 U/L; triglycerides > 156 mg/dL; fibrinogen ≤ 360 mg/dL) plus documentation of inadequate response to high‑dose IV glucocorticoids.

Denial Risk

Planned inpatient admission solely for administration not allowed

Requests that include a planned inpatient admission solely for the purpose of administering Gamifant (emapalumab) will not meet coverage criteria and are a denial risk.

Billing Rule

Dosing per FDA label

Dosing for Gamifant (emapalumab, HCPCS J9210) must be in accordance with the United States FDA‑approved labeling. Deviations from the approved dosing regimen may affect coverage decisions and authorization.

Applicable Codes

Drug HCPCSHCPCSCovered

J9210

Injection, emapalumab-lzsg, 1 mg

Relevant Diagnosis Codes (for reference)ICD-10

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

Clinical Evidence

53.8%HLH/MAS complete response (pooled studies): Complete response achieved in 53.8% (95% CI: 37.2, 69.9)

The pivotal trial program (NI-0501-04 and follow-up/compassionate use cohorts) demonstrated rapid disease control enabling many patients to proceed to hematopoietic stem cell transplantation (about 65% proceeded to HSCT with high engraftment and post‑HSCT event‑free survival). Common adverse events reported in the pre‑conditioning period included infections (56%) and infusion-related reactions (~27%), along with hypertension and pyrexia; viral infections (including CMV) and rash were among the most frequent reactions in HLH/MAS studies.

Background and Definitions

Primary HLH is a rare, often infant‑onset hyperinflammatory syndrome for which emapalumab provides targeted IFNγ neutralization to reduce pathogenic inflammation. Clinically, emapalumab is used as part of induction/maintenance to control disease and serve as a bridge to hematopoietic stem cell transplantation in eligible patients. The safety profile includes an increased risk of infections (bacterial, fungal, viral), infusion‑related reactions, and other events (e.g., hypertension, pyrexia); serious events and fatalities in trials were generally consistent with complications of HLH.

Term	Definition
MAS
Macrophage activation syndrome, a form of HLH occurring in rheumatic diseases such as Still's disease, including systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease.
HLH-2004 diagnostic criteria
Diagnostic framework requiring five of eight criteria (fever; splenomegaly; bicytopenia; hypertriglyceridemia and/or hypofibrinogenemia; hemophagocytosis; low or absent natural killer cell activity; hyperferritinemia; high soluble IL-2 receptor); diagnosis requires five of these eight criteria unless family history or genetic test is consistent with HLH.

Revision History

2026-04-01addedLatest

Effective date set to April 1, 2026 for this policy version.

2026-04-01revised

Removed content/language pertaining to Indiana and Louisiana and removed language indicating the policy did not apply to Indiana; archived previous policy versions CS2026D0077P and CSIND0077.07.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyGamifant (Emapalumab-Lzsg) medical benefit drug policy

Policy CodePolicy CS2026D0077Q

Change TypeApplication/state applicability updates; archived prior versions

Effective DateApr 1, 2026

Next Review Date

On This Page

Inpatient admission restriction: Provider does not request a planned inpatient admission for the sole purpose of administering Gamifant

Dosing is in accordance with the United States Food and Drug Administration approved labeling

Initial authorization will be for no more than 12 months12 months

OpenPayer

Gamifant (Emapalumab-Lzsg) medical benefit drug policy

Coverage Summary

Continuation / Reauthorization Criteria

Not Medically Necessary / Exclusions

Provider Actions / Prior Authorization Requirements

Applicable Codes

Clinical Evidence

Background and Definitions

Clinical Thresholds

Revision History