Brand Name



Interferon gamma (IFNγ) blocking antibody

FDA Indication

Hemophagocytic lymphohistiocytosis†,$


Emapalumab is an interferon gamma (IFN-γ)-blocking antibody approved as a breakthrough therapy for the treatment of patients with primary (familial) hemophagocytic lymphohistiocytosis (HLH) and refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy. It is intended for administration until a hematopoietic stem cell transplantation (HSCT) cure is achieved or unacceptable toxicity occurs.

Primary HLH is a rare genetic hyperinflammatory “cytokine storm” syndrome characterized by uncontrolled overactivation of the immune system resulting in hypersecretion of interferon gamma (IFNγ).85-87 Activation of T lymphocytes and macrophages, anemia, thrombocytopenia, neurologic signs and symptoms, multi-organ dysfunction, and a high mortality rate characterize the syndrome.85-87 Patients with HLH are at increased risk of developing leukemia and lymphoma.88 Approximately 40%–60% of cases are caused by mutations in the PRF1 or UNC13D genes.86,88 Conventional drugs for primary HLH have included antithymocyte globulin, corticosteroids, chemotherapy, and cyclosporine.85-87 HSCT remains the only curative therapy.

Emapalumab is a recombinant IFNγ-targeted IgG1 monoclonal antibody produced in Chinese hamster ovary cells.3 It binds to and neutralizes IFN-γ causing an associated reduction in the production of chemokine CXCL9. Consistent with the pharmacology of IFN-γ blockade, emapalumab is labeled with warnings regarding the development of severe infections.3 Emapalumab therapy requires that patients receive prophylaxis against Herpes zoster virus and Pneumocystis jiroveci fungal infections, as well as tuberculosis when clinically warranted.3 By countering the activity of IFN-γ, emapalumab may normalize cytokine-suppressed CYP450 enzyme production, changing the metabolism of some co-administered drugs over time.

Emapalumab is given as a 1-mg/kg IV infusion over 1 hour twice weekly, every 3–4 days.3 Besides infection, administration is associated with hypertension (41%), infusion-related reactions (27%), pyrexia (24%), septic shock, gastrointestinal hemorrhage, multiple organ dysfunction, and the development of antidrug antibodies.3 Emapalumab pharmacokinetics vary between and within patients, and as a function of time. The half-life of elimination is ~22 days in healthy subjects but ranges from 2.5 to 18.9 days in patients with HLH.3

The efficacy of emapalumab was evaluated in a multicenter, open-label, single-arm trial (NCT01818492) in 27 pediatric patients with suspected or confirmed primary HLH.3 A genetic mutation known to cause HLH was present in 82% of patients—the most frequent being FHL3-UNC13D (26%), FHL2-PRF1 (19%), and those associated with Griscelli syndrome type 2 (partial albinism with immunodeficiency) presumably due to RAB27A gene mutations (19%).3,88 The overall response rate at the end of treatment was 63% (17/27 patients), and 70% of patients (19/27) survived to proceeded to HSCT.3 The average wholesale price listed for 50 mg of emapalumab is $4453.20.89

Further Reading in Goodman & Gilman’s