CurrentUnitedHealthcarePolicy CSPA2025D0077I

Medical Benefit Drug Policy

UnitedHealthcare Medical Benefit Drug Policy for Gamifant (emapalumab-lzsg) applicable only to Pennsylvania members; defines medical necessity criteria for primary HLH and HLH/MAS in Still's disease (sJIA/AOSD), authorization durations, dosing alignment with FDA labeling, and applicable HCPCS/ICD-10 codes.

Policy Summary

PayerUnitedHealthcare

PolicyMedical Benefit Drug Policy

Policy CodePolicy CSPA2025D0077I

Change TypeRevised criteria; added HLH/MAS indication; code updates

Effective DateNov 1, 2025

Next Review Date

Key ActionSubmit medical records (chart notes, lab values) confirming required diagnostic criteria and other coverage elements (dexamethasone coadministration, transplant candidacy where required).

POLICY UPDATE CHANGES

Revised medical necessity criteria for Primary HLH including expanded example genes (added RAB27A, STX11, STXBP2), removal of fever temperature threshold, clarified NK cell activity wording, corrected ferritin units to mcg/L, and broadened examples of conventional HLH therapy.

Added coverage language indicating Gamifant is medically necessary for HLH/MAS in Still's disease (sJIA/AOSD) with inadequate response to high-dose glucocorticoids.

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; archived previous policy version CSPA2025D0077I.

2Indications with criteria (Primary HLH; HLH/MAS in Still's disease)

6 mo

Max authorization per request (primary HLH)

12 moInitial/reauthorization duration (HLH/MAS)

3ICD-10 codes listed

Coverage Summary

Coverage stance: covered_with_criteria. Scope: UnitedHealthcare Medical Benefit Drug Policy for Gamifant (emapalumab-lzsg) applicable only to Pennsylvania members. Subject: Gamifant (emapalumab-lzsg) coverage for HLH/MAS (Pennsylvania only). Policy number: CSPA2025D0077I. Effective date: 2025-11-01. Note: This policy applies to Pennsylvania members only. The policy defines medical necessity criteria and authorizations for two covered indications: Primary HLH (familial/genetic primary hemophagocytic lymphohistiocytosis meeting genetic or HLH diagnostic criteria) and HLH/MAS in Still's disease (MAS occurring with systemic juvenile idiopathic arthritis or adult-onset Still's disease after inadequate response to high‑dose IV glucocorticoids).

Quick threshold summary

Ferritin — primary HLH>= 500 mcg/L

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

Cytopenia cutoffs (require two of three)Hemoglobin < 9 g/dL; Platelets < 100 x10^9/L; Neutrophils < 1 x10^9/L

Triglycerides / Fibrinogen (HLH)Triglycerides >= 3 mmol/L (>= 265 mg/dL) or Fibrinogen <= 1.5 g/L

Mas lab cutoffs (need 2 of 4)Platelets <= 181 x10^9/L; AST > 48 U/L; Triglycerides > 156 mg/dL; Fibrinogen <= 360 mg/dL

Soluble CD25 (sIL-2R) threshold>= 2,400 U/mL or >= 2 SD above age-adjusted lab norms

Max authorization per request (primary HLH)6 mo

Initial / Reauthorization duration (HLH/MAS)Initial: up to 12 mo; Reauthorization: up to 12 mo (HLH primary requests limited to 6 mo per request)

Primary Hemophagocytic Lymphohistiocytosis (HLH) — Indication & Authorization

Gamifant ® is proven and medically necessary for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) when ALL of the following are met:

ALL of the following

- ANY of the following
  - Confirmation of a gene mutation known to cause primary HLH (e.g., PRF1, UNC13D, RAB27A, STX11, STXBP2).
  - Five-of-eight diagnostic criteria
    Fever
    Splenomegaly

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

Prior Authorization

Prior authorization: Documentation for HLH/MAS (Still's disease)

Submit medical records (chart notes, laboratory values) confirming the diagnosis and MAS criteria, plus documentation of inadequate response to high-dose IV glucocorticoids. Include chart notes and labs demonstrating MAS laboratory thresholds and prior steroid failure as part of the prior authorization request.

Provide chart notes and laboratory values confirming sJIA/AOSD diagnosis and MAS criteria (ferritin > 684 ng/mL and two of platelet ≤ 181 x 10^9/L, AST > 48 U/L, triglycerides > 156 mg/dL, fibrinogen ≤ 360 mg/dL).
Document inadequate response to high-dose intravenous glucocorticoids.

Documentation Required

Document dosing consistent with FDA label

Continuation / Reauthorization Criteria

HLH/MAS - Continuation of Therapy

For continuation/reauthorization of Gamifant in HLH/MAS:

ALL of the following

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

Exclusions / Not Medically Necessary

Situations where Gamifant is considered not proven or not medically necessary:

Exclusions

Secondary HLH not proven: Treatment of secondary HLH is not proven or medically necessary
Case-by-case review: Requests outside of these criteria will be reviewed for medical necessity on a case-by-case basis

Note

Applicable Codes

HCPCS (drug)HCPCSCovered

J9210

Injection, emapalumab-lzsg, 1 mg

ICD-10 (diagnoses referenced)ICD-10

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

Note: The ICD-10 diagnosis list has been expanded beyond D76.1 to include D76.2 and D76.3 per recent changes; these codes are provided for documentation and submission purposes only. Inclusion of a code does not by itself indicate coverage — benefit coverage depends on meeting the clinical medical necessity criteria in this policy.

Provider Actions & Requirements

Prior Authorization

Prior authorization: Required documentation (chart notes, labs)

Submit medical records (chart notes, laboratory values) confirming required diagnostic criteria (genetic confirmation or five HLH criteria for primary HLH; documented sJIA/AOSD and MAS lab criteria for MAS) and other coverage elements. Include documentation that Gamifant will be administered with dexamethasone, that the patient is a candidate for hematopoietic stem cell transplant when required, and that dosing aligns with FDA-approved labeling.

For primary HLH: genetic confirmation or documentation of five HLH criteria (see policy thresholds such as ferritin ≥ 500 mcg/L).
For MAS (sJIA/AOSD): ferritin > 684 ng/mL and two of the specified laboratory criteria.
Document dexamethasone coadministration and transplant candidacy where required; include complete chart notes and labs.

Documentation Required

Clinical Evidence

64.7%NI-0501-04 overall response at end of treatment

88.2%Pooled HLH response; median time to first response 8 days

53.8%MAS complete response (95% CI 37.2, 69.9)

Background/evidence summary: Clinical trials demonstrated meaningful response rates supporting emapalumab use in primary HLH (NI-0501-04: 64.7% overall response at end of treatment; pooled HLH response 88.2% with median time to first response 8 days) and in MAS related to Still's disease (pooled studies: complete response 53.8% [95% CI: 37.2, 69.9]) in patients with inadequate response to high‑dose glucocorticoids. Supporting information and references, including the package insert, were updated (package insert: June 2025).

Background & Definitions

Background: Primary HLH is a rare, typically infantile syndrome characterized by immune dysregulation and hyperinflammation with high mortality; MAS is a severe form of HLH that occurs most frequently in Still's disease (systemic juvenile idiopathic arthritis and adult-onset Still's disease). Emapalumab is an interferon‑gamma (IFNγ) neutralizing monoclonal antibody that binds and neutralizes IFNγ, decreasing IFNγ‑induced chemokines (e.g., CXCL9). The intended role of emapalumab is to control hyperinflammation and enable hematopoietic stem cell transplant when appropriate.

Revision History

2025-11-01revisedLatest

Revised medical necessity criteria for Primary HLH: expanded example genes (added RAB27A, STX11, STXBP2); removed explicit fever temperature threshold (now 'fever'); clarified NK cell activity wording; corrected ferritin units to mcg/L; broadened examples of conventional HLH therapy; replaced 'stem cell transplant' with 'hematopoietic stem cell transplant'; standardized authorization language to 'authorization will be for no more than 6 months'.

2025-11-01addedLatest

Added coverage language that Gamifant is medically necessary for HLH/MAS in Still's disease (sJIA/AOSD) with inadequate response to high‑dose intravenous glucocorticoids; initial authorization defined up to 12 months and continuation/reauthorization criteria require documentation of positive clinical response (reauthorization up to 12 months).

Policy Summary

PayerUnitedHealthcare

PolicyMedical Benefit Drug Policy

Policy CodePolicy CSPA2025D0077I

Change TypeRevised criteria; added HLH/MAS indication; code updates

Effective DateNov 1, 2025

Next Review Date

Key ActionSubmit medical records (chart notes, lab values) confirming required diagnostic criteria and other coverage elements (dexamethasone coadministration, transplant candidacy where required).

On This Page

Two cytopenias

Hemoglobin < 9 g/dL
Platelet count < 100 x 10^9/L
Neutrophils < 1 x 10^9/L

Laboratory abnormality

Hypertriglyceridemia (fasting triglycerides ≥ 3 mmol/L or ≥ 265 mg/dL)
Hypofibrinogenemia (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/mL or ≥ 2 standard deviations above age-adjusted laboratory norms

Patient has refractory, recurrent, or progressive disease OR intolerance to conventional HLH therapy (e.g., etoposide, corticosteroids, cyclosporine, anti-thymocyte globulin, methotrexate).

Gamifant ® will be administered with dexamethasone.

Patient is a candidate for hematopoietic stem cell transplant; Gamifant is being used as part of the induction or maintenance phase and is to be discontinued at initiation of conditioning for stem cell transplant.

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

Dosing Alignment: request must align with FDA-label dosing (including initial, escalation, and maintenance dose parameters).

Authorization will be for no more than 6 months per request (applies to both initial and renewal requests).

Authorization Duration Limits

Prior Authorization

Prior Authorization Required

Prior authorization required. Submit medical records confirming diagnostic criteria (genetic confirmation OR documentation of five HLH criteria). Authorization is limited to no more than 6 months per request. Dosing must align with FDA-approved labeling.

Authorization Duration Limits: Authorization will be granted for no more than 6 months per request for both initial and renewal requests.
Submit medical records confirming diagnostic criteria: genetic confirmation of primary HLH OR documentation of five of eight HLH diagnostic criteria prior to treatment.
Dosing Alignment: Dose and schedule must follow the FDA-approved labeling for emapalumab (including initial dosing, allowed dose escalations, and maintenance dosing).
Clinical documentation: Include prior therapy history demonstrating refractory, recurrent, or progressive disease or intolerance to conventional HLH therapies (e.g., etoposide, corticosteroids, cyclosporine, anti-thymocyte globulin, methotrexate).
Transplant candidacy: Provide documentation that patient is a candidate for hematopoietic stem cell transplant and plan for Gamifant use as induction/maintenance with discontinuation at initiation of conditioning.

Ensure and document that dosing is consistent with the United States FDA–approved labeling for Gamifant. The policy requires that dosing be in accordance with the FDA label; include dosing details in the clinical documentation submitted.

Document dosing schedule and amounts to show alignment with the FDA-approved labeling.
Policy does not specify dosing beyond requiring FDA-label compliance; include dosing rationale if deviating.

Denial Risk

Denial risk: Secondary HLH — at-risk indication

Requests for treatment of secondary HLH (infection-associated or other histiocytosis syndromes) are considered not proven / not medically necessary and are at risk for denial unless strong medical necessity justification is provided for case-by-case review. When applicable, reference the diagnosis codes below in the request and provide supporting documentation to justify medical necessity.

Affected diagnosis codes: D76.2 (Hemophagocytic syndrome, infection-associated), D76.3 (Other histiocytosis syndromes)

Documentation: Dosing alignment with FDA label

Ensure dosing is documented to align with the FDA-approved labeling and include the dosing regimen and rationale in submitted records. The policy requires dosing to be in accordance with U.S. FDA–approved labeling for both initial and continuation therapy.

Include the specific FDA-aligned dosing schedule and administered amounts in the clinical documentation.
State that dosing follows the FDA label; if adjustments are made, provide justification and supporting clinical data.

Prior Authorization

Prior authorization: Authorization duration limits by indication

Authorization durations vary by indication: for primary HLH, initial and renewal authorization will be for no more than 6 months per request; for HLH/MAS in Still's disease, initial and reauthorization may be up to 12 months (continuation requires documentation of positive clinical response).

Primary HLH: authorization limited to no more than 6 months per request (applies to initial and renewal).
HLH/MAS (Still's disease): initial authorization and reauthorization up to 12 months; continuation requires documentation of positive clinical response.

Billing Rule

Billing: HCPCS code for Gamifant

Use HCPCS code J9210 (injection, emapalumab-lzsg, 1 mg) as the administered drug code when billing. When requesting authorization or submitting documentation, reference J9210 where applicable so the service and dosing align with the policy requirements.

HCPCS (drug) code: J9210 — Injection, emapalumab-lzsg, 1 mg
Include J9210 on authorization and documentation submissions when applicable.

2025-11-01addedLatest

Applicable ICD-10 diagnosis codes list expanded to include D76.2 and D76.3.

2025-11-01revisedLatest

Updated Background, Clinical Evidence, FDA, and References sections (including package insert June 2025) and archived previous policy version CSPA2025D0077I.