ModifiedUnitedHealthcarePolicy CSLA2026D0077I

Gamifant Emapalumab Lzsg La Cs

UnitedHealthcare Medical Benefit Drug Policy for Gamifant (emapalumab-lzsg) applicable to Louisiana members, defining medical necessity criteria for primary HLH and HLH/MAS in Still's disease (sJIA/AOSD), dosing/administration constraints, authorization durations, and applicable HCPCS/ICD-10 codes. The policy was retired effective April 1, 2026.

Policy Summary

PayerUnitedHealthcare

PolicyGamifant Emapalumab Lzsg La Cs

Policy CodePolicy CSLA2026D0077I

Change TypeRetired; criteria revised/added

Effective DateJan 1, 2026

Next Review Date

Key ActionSubmit medical records (chart notes, laboratory values) confirming genetic testing or specified clinical/laboratory HLH or MAS criteria to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

Policy retired April 1, 2026; Louisiana plan membership disenrolled on Apr. 1, 2026.

Revised primary HLH medical necessity criteria on 01/01/2026, expanding listed pathogenic gene examples and relaxing/clarifying several diagnostic phraseologies.

Added HLH/MAS in Still's disease (sJIA/AOSD) coverage criteria including ferritin and specific lab thresholds and authorization periods (01/01/2026).

Added ICD-10 diagnosis codes D76.2 and D76.3 to Applicable Codes.

Updated Background, Clinical Evidence, FDA, and References sections to reflect current information (01/01/2026).

2Covered Indications (primary HLH; HLH/MAS in Still's disease)

Coverage Summary

Policy covers emapalumab (Gamifant) for primary HLH and for HLH/MAS in Still's disease (sJIA/AOSD) when the specified medical necessity criteria are met; treatment of secondary HLH is not considered proven or medically necessary. The policy applies only to Louisiana members and was retired effective April 1, 2026.

Primary Hemophagocytic Lymphohistiocytosis (HLH) — Initial Therapy Criteria

Primary Hemophagocytic Lymphohistiocytosis (HLH) - Medical Necessity

Emapalumab is proven and medically necessary when ALL of the following are met:

ALL of the following

Confirmation of primary HLH by ONE of
- Molecular confirmation: Confirmation of a gene mutation known to cause primary HLH (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2)
- OR Confirmation that five of the following clinical characteristics are present
  - Fever
  - Splenomegaly
  - Two of the following cytopenias in the peripheral blood
    Hemoglobin < 9 g/dL< 9 g/dL
    Platelet count < 100 x 10^9/L< 100 x 10^9/L
    Neutrophils < 1 x 10^9/L< 1 x 10^9/L
  - One of the following laboratory abnormalities
Medical records submission: Submission of medical records (e.g., chart notes, laboratory values) confirming one of the above
Conventional therapy failure/intolerance: Patient has refractory, recurrent or progressive disease or intolerance with conventional HLH therapy (e.g., etoposide, corticosteroids, cyclosporine, anti-thymocyte globulin, methotrexate)
Concomitant dexamethasone: Emapalumab will be administered with dexamethasone
Transplant candidacy: Patient is a candidate for hematopoietic stem cell transplant
Use relative to transplant conditioning: Emapalumab 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
FDA dosing: Dosing is in accordance with the United States Food and Drug Administration approved labeling
Follow FDA labeling for dose/schedule
Authorization duration: Authorization will be for no more than 6 months6 months
Maximum initial authorization duration

HLH/Macrophage Activation Syndrome (MAS) in Still's Disease — Initial Therapy Criteria

HLH/Macrophage Activation Syndrome (MAS) in Still's Disease (sJIA/AOSD) - Initial Therapy

Gamifant is medically necessary for HLH/MAS in Still's disease when ALL of the following are met:

ALL of the following

Medical records confirming diagnosis and labs
- Diagnosis: Confirmed or suspected diagnosis of systemic juvenile idiopathic arthritis (sJIA) or adult onset Still's disease (AOSD)
- Active MAS ferritin and labs: Diagnosis of active MAS with both of the following: Ferritin > 684 ng/mL AND two of the following laboratory criteriaFerritin > 684 ng/mL
- Two of the following laboratory criteria

Continuation of Therapy (Reauthorization) Criteria

HLH/MAS - Continuation of Therapy (Reauthorization)

Reauthorization requires ALL of the following:

ALL of the following

Positive clinical response: Documentation of a positive clinical response to Gamifant
FDA dosing adherence: Dosing is in accordance with the FDA approved labeling
Reauthorization duration: Reauthorization will be for no more than 12 months12 months

Unproven / Exclusions

Not Medically Necessary

Emapalumab is considered not proven or not medically necessary for:

ALL of the following

Secondary HLH exclusion: Treatment of secondary HLH

Applicable Codes

Covered HCPCS (drug administration code referenced)HCPCSCovered

J9210

Injection, emapalumab-lzsg, 1 mg

Relevant ICD-10 diagnosis codes (listed for reference)ICD-10

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

Provider Actions & Billing Impact

Prior Authorization

Medical records submission required

Submit medical records (chart notes, laboratory values) confirming genetic testing or the specified clinical and laboratory HLH or MAS criteria to support medical necessity.

Affected codes: J9210, D76.1, D76.2, D76.3
Submit genetic testing showing a pathogenic HLH gene (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2) or documentation of five HLH clinical criteria or the MAS diagnostic thresholds (ferritin and lab criteria) as specified in policy.

Prior Authorization

Authorization duration limits

Initial authorizations are limited to 6 months for primary HLH and to 12 months for initial HLH/MAS therapy; reauthorization for HLH/MAS requires documentation of positive clinical response and is limited to up to 12 months.

Clinical Evidence

64.7%Primary HLH overall response at end of treatment (NI-0501-04)

88.2%Overall response (NI-0501-04); median time to first response 8 days

8 daysMedian time to first response (NI-0501-04)

53.8%MAS complete response (pooled studies); 95% CI: 37.2, 69.9

Key clinical evidence includes the NI-0501 series (NI-0501-04 and follow-up NI-0501-05) and pooled MAS studies (NI-0501-06 and NI-0501-14). NI-0501-04 showed overall response with rapid disease control (median time to first response 8 days) and allowed many patients to proceed to hematopoietic stem cell transplant (65% underwent transplant, engraftment 86.4%). Pooled MAS studies reported a 53.8% complete response. Notable adverse events across studies included infections (bacterial, fungal, viral, including CMV), infusion-related reactions, and other serious events (e.g., respiratory failure); some infections and serious events were reported as related to emapalumab in individual cases.

Background & Definitions

Emapalumab is an IFNγ-neutralizing monoclonal antibody indicated for primary HLH and for HLH/MAS in known or suspected Still's disease (sJIA/AOSD). The drug binds and neutralizes interferon gamma, lowering IFNγ-driven biomarkers (e.g., CXCL9). In clinical practice and trials emapalumab has been used to control disease activity as a bridge to hematopoietic stem cell transplant in patients with refractory, recurrent, or progressive primary HLH or in patients with HLH/MAS with inadequate response to glucocorticoids.

MAS (macrophage activation syndrome) is a form of HLH that occurs in Still's disease, including systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD).

HLH (hemophagocytic lymphohistiocytosis) is an immune dysregulation and hyperinflammation syndrome; diagnostic criteria per HLH-2004 require five of eight clinical or laboratory features unless a molecular diagnosis is present.

Revision History

2026-04-01retirementLatest

Policy retired effective April 1, 2026; Louisiana plan membership disenrolled on April 1, 2026.

2026-01-01policy_revision

Revised primary HLH medical necessity criteria: expanded example gene list to include RAB27A, STX11, STXBP2; removed temperature threshold for fever; clarified NK cell activity wording; broadened examples of conventional therapy; replaced 'stem cell transplant' with 'hematopoietic stem cell transplant'; authorization language standardized (up to 6 months for primary HLH).

2026-01-01policy_addition