Gamifant (emapalumab-lzsg) coverage
Defines medical necessity, dosing, and authorization criteria for Gamifant (emapalumab-lzsg) for treatment of primary hemophagocytic lymphohistiocytosis (HLH) and HLH/Macrophage Activation Syndrome (MAS) in Cigna-administered health plans.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) was added as a condition of approval.
Documentation is required where noted in the criteria as [documentation required]; documentation may include chart notes, laboratory tests, claims records, and/or other information.
Coverage and Medical Necessity Criteria
Initial therapy criteria
Covered when ONE of the following is met (1 or 2):
HLH/MAS
ALL of the following
- A: Confirmed or suspected systemic juvenile idiopathic arthritis or adult‑onset Still's disease (HLH/MAS is a form of secondary HLH).
- B: Prior to treatment, ferritin > 684 ng/mL AND at least TWO of the following diagnostic criteria at baseline [documentation required]: i) platelets < 181 x10^9/L; OR ii) AST > 48 U/L; OR iii) fasting triglyceride > 156 mg/dL; OR iv) fibrinogen < 360 mg/dL.
- C: Meets ONE of: i) inadequate response or intolerance to high‑dose IV corticosteroids per prescriber; OR ii) prior receipt of Gamifant.
- D: Medication is prescribed by, or in consultation with, a hematologist, oncologist, immunologist, rheumatologist, or physician who specializes in hemophagocytic lymphohistiocytosis or related disorders.
Dosing: approve up to a maximum dose of 10 mg/kg IV, not more frequently than once daily.
Reauthorization Therapy
Reauthorization (continuation) criteria — continuation is considered medically necessary when ALL the following are met:
Reauthorization
- 1. Documentation of clinical response: improvement in any of the clinical or laboratory parameters used to demonstrate evidence of active disease on initial authorization, but with evidence of residual active disease.
- 2. Dose titration has occurred to the minimum dose and frequency needed to achieve sustained clinical effect as recommended by FDA labeling of emapalumab‑lzsg (Gamifant).
Any use of Gamifant that is not specifically described in the policy’s approved indications may be denied. Per the policy, "Any other use is considered experimental, investigational, or unproven." Providers requesting coverage for indications outside the criteria in this document should be aware such requests are subject to denial.
Use of Gamifant outside the specified primary HLH or HLH/MAS criteria in this policy is considered not medically necessary and is treated as experimental/investigational. Requests that do not meet the defined diagnostic and documentation requirements for these conditions may be denied.
Billing and Coding
| J9210 | Injection, emapalumab-lzsg, 1 mg |
Provider Actions, Prior Authorization, and Documentation
Prior Authorization Required
Prior authorization is required and enrollment must demonstrate that the patient meets the medical necessity criteria for primary HLH or HLH/MAS. Approval should include documentation supporting diagnosis and prior therapies where indicated.
- Prior authorization required prior to initiation of Gamifant (emapalumab-lzsg).
- Medication must be prescribed by, or in consultation with, an appropriate specialist (hematologist, oncologist, immunologist, transplant specialist, rheumatologist, or physician specializing in HLH or related disorders).
- Dosing limits: up to a maximum of 10 mg/kg IV per dose; frequency not more than twice weekly for primary HLH (once every 3–4 days) and not more frequently than once daily for HLH/MAS.
Prior Therapy / Step Requirements
For primary HLH, Gamifant is covered when disease is refractory, recurrent, or progressive on conventional HLH therapy or when intolerance to conventional therapy is documented. For HLH/MAS, coverage requires documented baseline laboratory criteria and either inadequate response or intolerance to high‑dose IV corticosteroids or prior receipt of Gamifant.
- Primary HLH: documented molecular genetic diagnosis or other criteria as required by the medical necessity section [documentation required].
- HLH/MAS: ferritin > 684 ng/mL and at least two of the specified baseline diagnostic criteria [documentation required].
- Evidence of prior therapy failure or intolerance as specified in the criteria (e.g., inadequate response to high‑dose IV corticosteroids).
Documentation Requirements
Documentation is required where noted in the criteria (marked [documentation required]). Acceptable documentation may include chart notes, laboratory results, genetic testing reports, procedure and hospital records, and claims records. Documentation should explicitly support the diagnosis, baseline lab values, prior treatments and response or intolerance, specialty consultation, and dosing.
- Genetic/molecular testing showing pathogenic variants for primary HLH when applicable [documentation required].
- Baseline laboratory values for HLH/MAS (ferritin, platelets, AST, fasting triglycerides, fibrinogen) [documentation required].
- Clinical notes documenting inadequate response or intolerance to prior therapies when required by the criteria [documentation required].
Unapproved Indications
Any use of Gamifant (emapalumab-lzsg) for indications other than primary hemophagocytic lymphohistiocytosis or HLH/MAS as specified in this policy is considered experimental, investigational, or unproven and may be denied.
- Codes: J9210 (Injection, emapalumab-lzsg, 1 mg) — uses outside the specified indications are not covered.
- Requests for off‑label or other unlisted indications should include supporting peer‑reviewed evidence; absence of such evidence may result in denial.
Background
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by prolonged fever, cytopenias, hepatosplenomegaly, markedly elevated inflammatory markers (including ferritin), and risk of multi‑organ failure. HLH can be primary (genetic; diagnosed by pathogenic germline variants or by meeting diagnostic criteria from the Histiocyte Society) or secondary, where it arises in association with triggers such as rheumatologic disease—referred to as macrophage activation syndrome (MAS). The pathophysiology involves excessive immune activation with interferon‑gamma (IFNγ) playing a central role; Gamifant is an anti‑IFNγ monoclonal antibody developed to target this pathway.
Definitions
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