Last Review Date: 08/05/2025

Date of Origin: 01/03/2019

Dates Reviewed: 01/2019, 01/2020, 01/2021, 01/2022, 01/2023, 01/2024, 03/2025, 08/2025

1. Length of Authorization

• Initial: Prior authorization validity will be provided initially for 6 months.
• Renewal: Prior authorization validity may be renewed every 6 months thereafter.

2. Dosing Limits

         Max Units (per dose and over time) [HCPCS Unit]:

• 9250 billable units per 30 days

3. Initial Approval Criteria

Coverage is provided in the following conditions:

     Universal Criteria ¹

• Patient has been evaluated and screened for the presence of latent tuberculosis (TB) infection prior to initiating treatment and will receive ongoing monitoring for the presence of TB during treatment; AND
• Providers will monitor and consider prophylaxis in patients for Herpes Zoster, Pneumocystis Jirovecii, and fungal infections; AND
• Patient does not have an active infection, including clinically important localized infections that are favored by interferon-gamma neutralization (e.g., infections caused by mycobacteria, Histoplasma Capsulatum, etc.); AND
• Must not be administered concurrently with live or live attenuated vaccines; AND

Primary Hemophagocytic Lymphohistiocytosis (HLH) † Ф ^1,3-7

• Patient has a definitive diagnosis of HLH as indicated by the following:
  • Patient diagnosis of primary HLH based on identification of biallelic pathogenic gene variants from molecular genetic testing (e.g., PRF1, UNC13D, STX11, or STXBP2) or a family history consistent with primary HLH; OR
  • Patient has at least FIVE of the following eight documented criteria:
    • Prolonged fever (> 7 days)
    • Splenomegaly
    • Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 x 10⁹/L, neutrophils < 1 x 10⁹/L)
    • Hypertriglyceridemia (fasting triglycerides > 3 mmol/L or ≥ 265 mg/dL) and/or hypofibrinogenemia (≤ 1.5 g/L)
    • Hemophagocytosis in bone marrow, spleen, or lymph nodes with no evidence of malignancy
    • Low or absent NK-cell activity
    • Ferritin ≥ 500 mcg/L
    • Soluble CD25 (aka soluble IL-2Rα receptor) ≥ 2400 U/mL; AND

• Patient has active, primary disease that is refractory, recurrent, or progressive during treatment with conventional HLH therapy (e.g., dexamethasone, etoposide, cyclosporine A, anti-thymocyte globulin, etc.) unless patient is intolerant to conventional HLH therapy; AND
• Patient has NOT received hematopoietic stem cell transplant (HSCT)*; AND
• Used in combination with dexamethasone (Note: Patients currently on oral cyclosporine A, or intrathecal methotrexate and/or glucocorticoids may continue on therapy while treated with emapalumab)

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) † Ф ¹

• Patient has a definitive diagnosis of HLH/MAS as indicated by BOTH of the following:
  • Ferritin >684 ng/mL; AND
  • At least 2 of the following:
    • Platelet count ≤181×10⁹/L
    • AST >48 U/L
    • Triglycerides >156 mg/dL
    • Fibrinogen levels ≤360 mg/dL; AND
• Patient has known or suspected diagnosis of Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA) or Adult Onset Still’s Disease (AOSD); AND
• Patient has had an inadequate response or intolerance to high-dose intravenous (IV) glucocorticoids OR has experience recurrent MAS

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), etc. identified in section III; AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: serious infections (including mycobacteria, Herpes Zoster virus, and Histoplasma Capsulatum), infusion-related reactions (including drug eruption, pyrexia, rash, erythema, and hyperhidrosis), etc.; AND
• Patient is receiving ongoing monitoring for adenovirus, EBV, and CMV viruses as clinically indicated; AND

Primary Hemophagocytic Lymphohistiocytosis (HLH) ^1,4,5

• Patient continues to require therapy for treatment of HLH (e.g., until HSCT is performed or unacceptable toxicity); AND
• Patient experienced a disease improvement in HLH abnormalities as evidenced by one of the following:
  • Complete response defined as normalization of all HLH abnormalities (i.e., no fever, no splenomegaly, neutrophils > 1x10⁹/L, platelets > 100x10⁹/L, ferritin < 2,000 μg/L, fibrinogen > 1.50 g/L, D-dimer < 500 μg/L, normal CNS symptoms, no worsening of sCD25 > 2-fold baseline); OR
  • Partial response defined as normalization of ≥ 3 HLH abnormalities (including CNS abnormalities); OR
  • HLH improvement defined as improvement by at least 50% from baseline of ≥ 3 HLH clinical and laboratory criteria (including CNS involvement); OR
• Dose escalation (up to the maximum dose and frequency specified in the Dosage/Administration table below) requests based on clinical and laboratory parameters being interpreted as an unsatisfactory response are defined as at least ONE of the following:
  • Fever – persistence or recurrence
  • Platelet count
    • If baseline < 50,000/mm³ and no improvement to >50,000/mm³
    • If baseline > 50,000/mm³ and less than 30% improvement
    • If baseline > 100,000/mm³ and decrease to < 100,000/mm³
  • Neutrophil count
    • If baseline < 500/mm³ and no improvement to > 500/mm³
    • If baseline > 500 -1000/mm³ and decrease to < 500/mm³
    • If baseline 1000-1500/mm³ and decrease to < 1000/mm³
  • Ferritin (ng/mL)
    • If baseline ≥ 3000 ng/mL and < 20% decrease
    • If baseline < 3000 ng/mL and any increase to > 3000 ng/mL
  • Splenomegaly – any worsening
  • Coagulopathy (both D-dimer and fibrinogen must apply)
    • D-Dimer
      • If abnormal at baseline and no improvement
    • Fibrinogen (mg/dL)
      • If baseline levels ≤ 100 mg/dL and no improvement
      • If baseline levels > 100 mg/dL and any decrease to < 100 mg/dL

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) ¹

• Patient continues to require therapy for treatment of HLH; AND
  • Patient experienced a complete response (CR) as evidenced by the following:
    • Clinical resolution of MAS signs and symptoms (a visual analogue scale (VAS), of ≤1 cm [range 0 to 10 cm]); AND
    • The following 7 laboratory parameter endpoints:
      • WBC count and platelet count above the lower limit of normal (LLN); AND
      • LDH, AST and ALT below 1.5 times the upper limit of normal (ULN); AND
      • Fibrinogen >100 mg/dL; AND
      • Ferritin levels decreased ≥80% from values at screening or baseline (whichever initial value was higher) or < 2000 ng/mL, whichever was lower; OR
  • Patient has had unsatisfactory improvement in clinical condition, as assessed by a healthcare provider and requires dose escalation (up to the maximum dose and frequency specified in the Dosage/Administration table below)

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9210 ­− Injection, emapalumab-lzsg, 1 mg; 1 billable unit = 1 mg

NDC:

• Gamifant 10 mg/2 mL single-dose vial: 66658-0501-xx
• Gamifant 50 mg/10 mL single-dose vial: 66658-0505-xx
• Gamifant 100 mg/20 mL single-dose vial: 66658-0510-xx
• Gamifant 50 mg/2 mL single-dose vial: 66658-0522-xx
• Gamifant 100 mg/4 mL single-dose vial: 66658-0523-xx
• Gamifant 250 mg/10 mL single-dose vial: 66658-0524-xx
• Gamifant 500 mg/20 mL single-dose vial: 66658-0525-xx

7. References

1. Gamifant [package insert]. Waltham, MA; Sobi, Inc., June 2025. Accessed July 2025.
2. Jordan M, Locatelli F, Allen C, et al. A Novel Targeted Approach to the Treatment of Hemophagocytic Lymphohistiocytosis (HLH) with an Anti-Interferon Gamma (IFNγ) Monoclonal Antibody (mAb), NI-0501: First Results from a Pilot Phase 2 Study in Children with Primary HLH. Blood 2015 126:LBA-3
3. Zhang K, Astigarraga I, Bryceson Y, et al. Familial Hemophagocytic Lymphohistiocytosis. 2006 Mar 22 [Updated 2021 Sept 30]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1444/.
4. Jordan M, Allen C, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041. Epub 2011 Aug 9.
5. Ouachée-Chardin M, Elie C, de Saint Basile G, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006;117(4):e743.
6. McClain KL. Treatment and prognosis of hemophagocytic lymphohistiocytosis. In Newburger P (Ed), UpToDate. Last updated: May 6, 2022. Accessed on January 23, 2025. Available from: https://www.uptodate.com/contents/treatment-and-prognosis-of-hemophagocytic-lymphohistiocytosis?search=Treatment%20and%20prognosis%20of%20hemophagocytic%20lymphohistiocytosis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.
7. NovoImune SA. A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis. Available from: https://clinicaltrials.gov/ct2/show/NCT01818492?term=01818492&draw=1&rank=1. ClinicalTrials.gov Identifier: NCT01818492. Accessed January 2025.
8. Locatelli F, Jordan MB, Allen C, et al. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326.
9. De Benedetti F, Grom AA, Brogan PA, et al. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann Rheum Dis. 2023 Jun;82(6):857-865. doi: 10.1136/ard-2022-223739. Epub 2023 Mar 31. PMID: 37001971; PMCID: PMC10314091.
10. Grom A, Ullman U, Mahmood A, et al. OP0207 EFFICACY AND SAFETY OF EMAPALUMAB IN PATIENTS WITH MACROPHAGE ACTIVATION SYNDROME IN STILL'S DISEASE: RESULTS FROM A POOLED ANALYSIS OF TWO PROSPECTIVE TRIALS. Annals of the Rheumatic Diseases,Volume 84, Supplement 1, 2025, Pages 172-173, ISSN 0003-4967, https://doi.org/10.1016/j.ard.2025.05.219.
11. Hines MR, von Bahr Greenwood T, Beutel G, et al. Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults. Crit Care Med. 2022 May 1;50(5):860-872. doi: 10.1097/CCM.0000000000005361. Epub 2021 Oct 5. PMID: 34605776.
12. La Rosée P, Horne AC, Hines M, et al; Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 2019; 133 (23): 2465–2477. doi: https://doi.org/10.1182/blood.2018894618.
13. Wu, Y., Sun, X., Kang, K. et al. Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms. J Hematol Oncol 17, 106 (2024). https://doi.org/10.1186/s13045-024-01621-x.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A