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Indication

Gamifant® (emapalumab-lzsg) is an interferon gamma (IFNγ)–blocking antibody indicated for the treatment of adult and pediatric (newborn and older) patients with primary... hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy.

Important Safety Information
Infections

Before initiating Gamifant, patients should be evaluated for infection, including latent tuberculosis (TB)... Prophylaxis for TB should be administered to patients who are at risk for TB or known to have a positive purified protein derivative (PPD) test result or positive IFNγ release assay.

Indication

Gamifant® (emapalumab-lzsg) is an interferon gamma (IFNγ)–blocking antibody indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy.

Important Safety Information

Infections

Before initiating Gamifant, patients should be evaluated for infection, including latent tuberculosis (TB). Prophylaxis for TB should be administered to patients who are at risk for TB or known to have a positive purified protein derivative (PPD) test result or positive IFNγ release assay.

During Gamifant treatment, patients should be monitored for TB, adenovirus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) every 2 weeks and as clinically indicated.

Patients should be administered prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections prior to Gamifant administration.

Increased Risk of Infection With Use of Live Vaccines

Do not administer live or live attenuated vaccines to patients receiving Gamifant and for at least 4 weeks after the last dose of Gamifant. The safety of immunization with live vaccines during or following Gamifant therapy has not been studied.

Infusion-Related Reactions

Infusion-related reactions, including drug eruption, pyrexia, rash, erythema, and hyperhidrosis, were reported with Gamifant treatment in 27% of patients. In one-third of these patients, the infusion-related reaction occurred during the first infusion.

Adverse Reactions

In the pivotal trial, the most commonly reported adverse reactions (≥10%) for Gamifant included infection (56%), hypertension (41%), infusion-related reactions (27%), pyrexia (24%), hypokalemia (15%), constipation (15%), rash (12%), abdominal pain (12%), CMV infection (12%), diarrhea (12%), lymphocytosis (12%), cough (12%), irritability (12%), tachycardia (12%), and tachypnea (12%).

Additional selected adverse reactions (all grades) that were reported in less than 10% of patients treated with Gamifant included vomiting, acute kidney injury, asthenia, bradycardia, dyspnea, gastrointestinal hemorrhage, epistaxis, and peripheral edema.

Click here for full Prescribing Information for Gamifant.

You may also contact Sobi at medinfo.us@sobi.com or 866-773-5274.

References

  1. Wang H, Yang Y. The complex and central role of interferon-γ in graft-versus-host disease and graft-versus-tumor activity. Immunol Rev. 2014; 258(1):30-44. doi:10.1111/imr.12151.
  2. Mordan M, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood. 2004;104(3): 735-743. doi: https://doi.org/10.1182/blood-2003-10-3413.
  3. Ealick SE, Cook WJ, Vijay-Kumar S, et al. Three-dimensional structure of recombinant human interferon-γ. Science. 1991;252(5006):698-702.
  4. Tau G, Rothman P. Biologic functions of the IFN-γ receptors. Allergy. 1999; 54(12):1233-1251.
  5. Zaidi MR, Merlino G. The two faces of interferon-γ in cancer. Clin Cancer Res. 2011;17(19):6118-6124.
  6. Kak G, Raza M, Tiwari B. Interferon-gamma (IFN-γ): exploring its implications in infectious diseases. BioMol Concepts. 2018; 9:64-79. https://dio.org/10/1515/bmc-2018-0007.
  7. Pestka S, Krause C, Walter M. Interferons, interferon-like cytokines, and their receptors. Immunol Rev. 2004; 202:8-32.
  8. Gamifant [prescribing information]. Stockholm, Sweden: Swedish Orphan Biovitrum AB.
  9. Sepulveda F, de Saint Basile G. Hemophagocytic syndrome: primary forms and predisposing conditions. Curr Opin Immunol. 2017; 49:20-26. http://dx.doi.org/10.1016/j.coi.2017.08.004.
  10. Dustin ML. The immunological synapse. Cancer Immunol Res. 2014;2(11):1023-1033.
  11. Westburg. T-Cell Mediated Cytotoxicity. Available at: https://www.westburg.eu/immunotherapy-for-cancer/active-immunotherapy/t-cell-mediated-cytotoxicity. Accessed July 21, 2020.
  12. Wissinger E. CD8+ T Cells. Imperial College London, UK. British Society for Immunology. Available at: https://www.immunology.org/public-information/bitesized-immunology/c%C3%A9lulas/cd8-t-cells. Accessed July 21, 2020.
  13. Morimoto A, Nakazawa Y, Ishii E. Hemophagocytic lymphohistiocytosis: pathogenesis, diagnosis, and management. Pediatr Int. 2016; 58:817-825. doi: 10.1111/ped.13064.
  14. Marsh RA, Haddad E. How I treat primary haemophagocytic lymphohistiocytosis. Br J Haematol. 2018;182(2):185-199. doi: 10.1111/bjh.15274.
  15. Tang Y, XU X, Song H, et al. Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine patter in children with haemophagocytic syndrome. Br J Haematol. 2008;143: 84-91. doi:10.1111/j.1365-2141.2008.07298.x.
  16. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-4052. doi: https://doi.org/10.1182/blood-2011-03-278127.
  17. Lehmberg K, Nichols KE, Henter J-I, et al. Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologica. 2015:100(8):997-1004.
  1. HOME
  2. Primary HLH
  3. IFNγ in primary HLH

IFNγ is a key cytokine in the immune system1

Interferon gamma (IFNγ) is the only type II interferon and plays an important role in cell communication during immune responses.1-5 During innate immune responses, IFNγ helps eliminate intracellular pathogens by activating macrophages and natural killer (NK) cells.1,3 During adaptive immune responses, IFNγ is responsible for both the differentiation and overproliferation of activated T cells.6,7

IFNγ can be produced by CD4+ T-helper type 1 (T1) cells, activated CD8+ T cells, NK cells, NK T cells, B cells, and antigen-presenting cells (APCs).1,7

IFNγ is a driver of hyperinflammation

Preclinical data suggest that the cytokine IFNγ plays a central and upstream role in the pathogenesis of primary hemophagocytic lymphohistiocytosis (HLH). Massive overexpression of IFNγ leads directly to downstream hypercytokinemia and hyperinflammation.2,8,9

While downstream cytokines—including IL-10, IL-12, IL-18, anti-TNF, anti–M-CSF, and anti–GM-CSF—likely impact inflammatory symptoms, animal studies attempting to suppress such cytokines have not shown any positive impact.2

Video: the role of IFNγ in primary HLH See the full video
In primary HLH, genetic mutations prevent perforin pore formation needed for cell lysis

Genetic mutations disrupt immune function

In healthy individuals, APCs are recognized by cytotoxic CD8+ T cells, which bind to them to release perforin and granzymes into the immunological synapse space. Perforin creates pores in the target cell's plasma membrane, allowing the cytotoxic granzymes to enter and initiate lysis. In primary HLH, genetic mutations prevent perforin pore formation needed for cell lysis.10-12

See how IFNγ unleashes the storm

Click through to see how IFNγ drives the uncontrolled release of cytokines, which result in the rapidly progressive and life-threatening symptoms of untreated primary HLH.

IFNγ drives the uncontrolled release of cytokines, which result in the rapidly progressive and life-threatening symptoms of primary HLH.

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IFNγ activates a macrophage to release cytokines IFNγ activates a macrophage to release cytokines
IFNγ Guide

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Discover the storm

Primary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that mostly affects children, but can also occur in adults and teenagers.9,14,16,17

Gamifant reduces the inflammatory symptoms of primary HLH by neutralizing IFNγ.8

Dosing and Administration

Gamifant is given as an intravenous infusion twice per week until the patient no longer requires therapy for the treatment of HLH or until hematopoietic stem cell transplantation (HSCT) is performed.8

ORDERING GAMIFANT

Contact your Sobi Health Systems Director to understand Gamifant ordering options. Connect with your Reimbursement Manager for your individual patient's insurance coverage policy and reimbursement pathway.

Help through the storm

Here you’ll find tools and resources to help your patients and their families.