INDICATIONS
Gamifant (emapalumab-lzsg) is an interferon gamma (IFNγ)-neutralizing 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.
- HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS.
IMPORTANT SAFETY INFORMATION
Infections
Gamifant may increase the risk of fatal and serious infections with pathogens including mycobacteria, herpes zoster virus... and histoplasma capsulatum. Do not administer Gamifant in patients with these infections until appropriate treatment has been initiated.
INDICATIONS
Gamifant (emapalumab-lzsg) is an interferon gamma (IFNγ)-neutralizing 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.
- HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS.
IMPORTANT SAFETY INFORMATION
Infections
Gamifant may increase the risk of fatal and serious infections with pathogens including mycobacteria, herpes zoster virus, and histoplasma capsulatum. Do not administer Gamifant in patients with these infections until appropriate treatment has been initiated.
In patients with primary HLH receiving Gamifant in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed in 32% of patients.
In patients with HLH/MAS in Still’s disease receiving Gamifant in clinical trials, serious infections such as pneumonia, cytomegalovirus infection, cytomegalovirus infection reactivation, and sepsis were observed in 13% of patients.
Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating Gamifant. Administer tuberculosis prophylaxis to patients at risk for tuberculosis or known to have a positive purified protein derivative (PPD) test result.
Consider prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infection while receiving Gamifant. Employ surveillance testing during treatment with Gamifant.
Closely monitor patients receiving Gamifant for signs or symptoms of infection, promptly initiate a complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
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 in patients with primary HLH, 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.
Infusion-related reactions in patients with HLH/MAS in Still’s disease, including pyrexia, headache, paresthesia, bone pain, pruritic rash, and peripheral coldness, were reported with Gamifant treatment in 13% of patients. Infusion-related reactions were reported as mild in 8% of patients and as moderate in 5% of patients.
Monitor patients for infusion-related reactions, which can be severe. Interrupt the infusion for infusion reactions and institute appropriate medical management before continuing infusion at a slower rate.
Adverse Reactions
Primary HLH
Serious adverse reactions were reported in 53% of patients. The most common serious adverse reactions (≥3%) included infections, gastrointestinal hemorrhage, and multiple organ dysfunction. Fatal adverse reactions occurred in 2 (6%) of patients and included septic shock and gastrointestinal hemorrhage.
The most common adverse reactions were (≥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%).
HLH/MAS
Serious adverse reactions were reported in 12 patients (31%), with the most common serious adverse reaction being pneumonia (5%). Fatal adverse reactions occurred in two patients (5%) and included multiple organ dysfunction and circulatory shock.
The most common adverse reactions (≥10%) for Gamifant included viral infection (44%), rash (21%), anemia (18%), leukopenia (15%), thrombosis (15%), bacterial infections (13%), headache (13%), hyperglycemia (13%), infusion-related reactions (13%), abdominal pain (10%), hypertension (10%), pyrexia (10%), and thrombocytopenia (10%).
References
- Gamifant (emapalumab-lszg) prescribing information. Stockholm, Sweden: Sobi, Inc. 2022.
- Locatelli F, Jordan MB, Allen C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 2020;382(19):1811-1822. doi:10.1056/NEJMoa1911326
- Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-4052. doi:10.1182/blood-2011-03-278127
- Sepulveda FE, de Saint Basile G. Hemophagocytic syndrome: primary forms and predisposing conditions. Curr Opin Immunol. 2017;49:20-26. doi:10.1016/j.coi.2017.08.004
Gamifant® (emapalumab-lzsg) demonstrated efficacy and safety in a pivotal trial1
Gamifant® (emapalumab-lzsg) demonstrated efficacy and safety in a pivotal trial1
The safety and efficacy of Gamifant was evaluated in a multicenter, open-label, single-arm study.1,2
Safety
evaluated in 34 patients
Efficacy
evaluated in 27 patients
- Were treatment-naïve prior to receiving Gamifant
- Received Gamifant after conventional treatments attempted
Studied in patients with significant unmet need1
Patients enrolled in the Gamifant pivotal trial had either suspected or confirmed primary hemophagocytic lymphohistiocytosis (HLH) based on 5 of the 8 HLH-2004 criteria with no evidence of malignancy, molecular diagnosis, or family history consistent with primary HLH.
In addition, the treating physician assessed patients as having at least one of the following: refractory disease, recurrent disease, progressive disease, and/or intolerance to conventional therapy.
A diagnosis of primary HLH was suspected in 18% of patients based on the HLH-2004 diagnostic criteria with no evidence of malignancy. Diagnosis was genetically confirmed in 82% of patients.
The most frequent causative mutations were FHL3-UNC13D (MUNC 13-4) (26%), FHL2-PRF1 (19%), and Griscelli syndrome type 2 (19%).1
The median age of patients in the study was 1 year.
Patients ranged in age from 0.2 years to 13 years old.1
27 of 34 patients received conventional therapy prior to enrollment, with a median of 3 prior agents.
Prior regimens included combinations of dexamethasone, etoposide, cyclosporine A, and antithymocyte globulin.1
The median duration of Gamifant treatment was 59 days.
Duration of treatment ranged from 4 to 245 days in 34 patients studied for safety.1
Primary endpoint1
The primary endpoint was overall response rate (ORR) at end of treatment. ORR was defined as achievement of either complete or partial response or HLH improvement and evaluated using an algorithm of objective clinical and laboratory parameters.
Complete response
defined as normalization of all HLH abnormalities (ie, no fever, no splenomegaly, neutrophils >1x109/L, platelets >100x109/L, ferritin <2000 μg/L, fibrinogen >1.50 g/L, D-dimer <500 μg/L, normal CNS symptoms, no worsening of soluble CD25* >2-fold baseline)
*Soluble CD25 is also referred to as soluble interleukin-2 receptor.
Partial response
defined as normalization of
≥3 HLH abnormalities
HLH improvement
defined as ≥3 HLH abnormalities improved by at least 50% from baseline
Key secondary endpoints
Secondary efficacy endpoints included the time to response, duration of response, and the number of patients proceeding to transplant.2
see the results
Check out the Investigating HLH podcast to hear Dr Michael B. Jordan discuss the Gamifant pivotal trial.
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