Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 8/21/2023

Drug Summary

What Is Gamifant?

Gamifant (emapalumab-lzsg) is an interferon gamma (IFN?) 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.

What Are Side Effects of Gamifant?

Gamifant may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • fever,
  • chills,
  • sweating,
  • itching,
  • lightheadedness,
  • nausea,
  • chest pain,
  • shortness of breath,
  • skin rash or redness,
  • night sweats,
  • loss of appetite,
  • weight loss,
  • tiredness,
  • warmth, redness, or painful sores on your skin,
  • cough,
  • mouth and throat ulcers,
  • cough with bloody mucus, and
  • new or worsening signs of infection

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Gamifant include:

Get medical help right away, if you have any of the symptoms listed above.

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Gamifant

The recommended starting dosage of Gamifant is 1 mg/kg as an intravenous infusion over 1 hour twice per week. Dexamethasone is administered concomitantly with Gamifant.

What Drugs, Substances, or Supplements Interact with Gamifant?

Gamifant may interact with CYP450 substrates. Tell your doctor all medications and supplements you use.

Gamifant During Pregnancy or Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Gamifant; it is unknown how it would affect a fetus. It is unknown if Gamifant passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Gamifant (emapalumab-lzsg) Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Drug Description


Emapalumab-lzsg is an interferon gamma (IFNγ) blocking antibody. Emapalumab-lzsg is produced in Chinese Hamster Ovary cells by recombinant DNA technology. Emapalumab-lzsg is an IgG1 immunoglobulin with a molecular weight of approximately 148 kDa.

GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion.

Each vial contains 10 mg/2 mL or 50 mg/10 mL emapalumab-lzsg at a concentration of 5 mg/mL. Each mL also contains the following inactive ingredients: L-Histidine (1.55 mg), L-Histidine monohydrochloride, monohydrate (3.14 mg), Polysorbate 80 (0.05 mg), sodium chloride (7.30 mg), and Water for Injection, USP.

Indications & Dosage


GAMIFANT is 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.


Recommended Dosing

The recommended starting dose of GAMIFANT is 1 mg/kg given as an intravenous infusion over 1 hour twice per week (every three to four days). Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria [see DOSAGE AND ADMINISTRATION].

Administer GAMIFANT until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity. Discontinue GAMIFANT when a patient no longer requires therapy for the treatment of HLH.

Monitoring To Assess Safety

Before Initiating GAMIFANT Treatment

Conduct testing for latent tuberculosis infections using the purified protein derivative (PPD) or IFNγ release assay and evaluate patients for tuberculosis risk factors prior to initiating GAMIFANT. Administer tuberculosis prophylaxis to patients at risk for tuberculosis, or known to have a positive PPD test result, or positive IFNγ release assay.

During GAMIFANT Treatment

Monitor for tuberculosis, adenovirus, EBV and CMV every 2 weeks and as clinically indicated.

Pre-Medications And Concomitant Medication Information


Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and for fungal infections prior to GAMIFANT administration.

Concomitant Medications

For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 to 10 mg/m² the day before GAMIFANT treatment begins. For patients who were receiving baseline dexamethasone, they may continue their regular dose provided the dose is at least 5 mg/m². Dexamethasone can be tapered according to the judgment of the treating physician [see Clinical Studies].

Dose Modification Based On Response

The GAMIFANT dose may be titrated up if disease response is unsatisfactory (see Table 1) [see CLINICAL PHARMACOLOGY]. After the patient’s clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response.

Table 1: Dose Titration Criteria

Treatment Day GAMIFANT Dose Criteria for Dose Increase
Day 1 Starting Dose of 1 mg/kg N/A
On Day 3 Increase to 3 mg/kg Unsatisfactory improvement in clinical condition, as assessed by a healthcare provider AND 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
From Day 6 onwards Increase to 6 mg/kg
From Day 9 onwards Increase to 10 mg/kg Assessment by a healthcare provider that based on initial signs of response, a further increase in GAMIFANT dose can be of benefit

Instructions For Preparation And Administration


GAMIFANT vials are for single-use only.

Prepare the solution for infusion as follows:

  • Calculate the dose (mg/kg), total volume (mL) of GAMIFANT required and the number of GAMIFANT vials needed based on patient actual body weight [see DOSAGE AND ADMINISTRATION].
  • Inspect GAMIFANT vials visually for particulate matter and discoloration prior to dilution. GAMIFANT is a clear to slightly opalescent, colorless to slightly yellow liquid. Do not administer if discolored or foreign particulate matter is present.
  • Withdraw the necessary amount of GAMIFANT solution and dilute with 0.9% Sodium Chloride Injection, USP to a maximum concentration of 2.5 mg/mL. Do not dilute product to less than 0.25 mg/mL.
  • Discard any unused portion left in the vial(s).
  • The diluted solution can be placed in either a syringe or an infusion bag, depending on the volume needed.
  • Use a gamma irradiated latex-free, polyvinyl chloride (PVC)-free syringe. Do not use with ethylene oxide-sterilized syringes.
  • Use a non-PVC polyolefin infusion bag.
  • Administer GAMIFANT diluted solution intravenously over 1 hour through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron in-line filter.
  • Do not infuse GAMIFANT concomitantly with other agents and do not add any other product to the infusion bag or syringe.
  • Do not store any unused portion of the infusion solution for reuse. Any unused product or waste material should be disposed of in accordance with local requirements.
Storage Of Diluted Solution

This product does not contain a preservative.

If not administered immediately:

  • Store the diluted solution of GAMIFANT under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of dilution.
  • If refrigerated, allow the diluted solution to come to room temperature prior to administration.
  • Do not freeze. Do not shake.


Dosage Forms And Strengths

GAMIFANT is a clear to slightly opalescent, colorless to slightly yellow preservative-free solution available as:

  • 10 mg/2 mL (5 mg/mL) in a single-dose vial
  • 50 mg/10 mL (5 mg/mL) in a single-dose vial
  • 100 mg/20 mL (5 mg/mL) in a single-dose vial

Storage And Handling

GAMIFANT (emapalumab-lzsg) injection is a sterile, clear to slightly opalescent, colorless to slightly yellow solution supplied in the following packaging configuration:

NDC 66658-501-01 – containing one 10 mg/2 mL (5 mg/mL) single-dose vial
NDC 66658-505-01 – containing one 50 mg/10 mL (5 mg/mL) single-dose vial
NDC 66658-510-01 – containing one 100 mg/20 mL (5 mg/mL) single-dose vial

Store GAMIFANT in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake. This product contains no preservative.

Manufactured by: Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden, U.S. License Number 1859. Distributed by:  Sobi Inc., 77 Fourth Avenue, 3rd Floor, Waltham, MA 02451-7559. Manufactured at: Patheon Italia S.p.A 2° Trav. SX Via Morolense, 5 03013-Ferentino Italy, Product of the United Kingdom. Revised: May 2022

Side Effects & Drug Interactions


The following adverse reactions are described elsewhere in the labeling:

  • Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in this section reflect exposure to GAMIFANT in which 34 patients with untreated primary HLH and previously treated patients with primary HLH (NCT01818492) received GAMIFANT at a starting dose of 1 mg/kg every 3 days with dose increases up to 10 mg/kg [see DOSAGE AND ADMINISTRATION and Clinical Studies]. The median duration of treatment with GAMIFANT was 59 days (range: 4 to 245 days) and the median cumulative dose was 25 mg/kg (range: 4 to 254 mg/kg).

The median age of study population was 1 year (range: 0.1 to 13 years), 53% were female, and 65% were Caucasian.

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 two (6%) of patients and included septic shock and gastrointestinal hemorrhage.

Disseminated histoplasmosis led to drug discontinuation in one patient. The most commonly reported adverse reactions (≥ 20%) were infections, hypertension, infusion-related reactions, and pyrexia. Adverse reactions reported in ≥ 10% of patients during treatment with GAMIFANT are presented in Table 2.

Table 2: Adverse Reactions Reported in ≥ 10% of Patients with Primary HLH

Adverse Reactions GAMIFANT (%)
(N = 34)
Infectionsa 56
Hypertensionb 41
Infusion-related reactionsc 27
Pyrexia 24
Hypokalemia 15
Constipation 15
Rash 12
Abdominal pain 12
Cytomegalovirus infection 12
Diarrhea 12
Lymphocytosis 12
Cough 12
Irritability 12
Tachycardia 12
Tachypnea 12
aIncludes viral, bacterial, fungal, and infections in which no pathogen was identified
bIncludes secondary hypertension
cIncludes events of drug eruption, pyrexia, rash, erythema, and hyperhidrosis

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, gastro-intestinal hemorrhage, epistaxis, and peripheral edema.


As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other emapalumab products may be misleading.

The immunogenicity of emapalumab-lzsg has been evaluated using an electrochemiluminescence-based immunoassay (ECLIA). A total of 64 subjects were evaluated for anti-therapeutic antibodies (ATAs) to emapalumab-lzsg after treatment with GAMIFANT. ATAs were detected in 3/64 subjects (5%) who received GAMIFANT.

Treatment-emergent ATAs were detected in 1/33 (3%) of patients in the primary HLH clinical trial. The ATAs in this patient were found to have neutralizing ability. One patient receiving GAMIFANT through compassionate use developed transient non-neutralizing treatment-emergent ATAs. In both of these patients, ATAs occurred within the first 9 weeks following the initiation of GAMIFANT treatment. In addition, one healthy subject tested positive for ATAs following a single dose of GAMIFANT. No evidence of an altered safety or efficacy profile was identified in the primary HLH patients who developed antibodies to emapalumab-lzsg.


Effect Of GAMIFANT On Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (such as IFNγ) during chronic inflammation. By neutralizing IFNγ, use of GAMIFANT may normalize CYP450 activities which may reduce the efficacy of drugs that are CYP450 substrates due to increased metabolism.

Upon initiation or discontinuation of concomitant GAMIFANT, monitor for reduced efficacy and adjust dosage of CYP450 substrate drugs as appropriate.

Warnings & Precautions


Included as part of the PRECAUTIONS section.



GAMIFANT may increase the risk of fatal and serious infections to include specific pathogens favored by IFNγ neutralization, including mycobacteria, Herpes Zoster virus, and Histoplasma Capsulatum.

Do not administer GAMIFANT in patients with infections caused by these pathogens until appropriate treatment has been initiated.

In 32% of patients receiving GAMIFANT in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed. The reported infections were viral (41%), bacterial (35%), fungal (9%), and the pathogen was not identified in 15% of cases.

Evaluate patients for tuberculosis risk factors and test for latent infection (PPD testing, PCR, or IFNγ release assay) 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 [see DOSAGE AND ADMINISTRATION].

Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infection to mitigate the risk to patients 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 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.

All infusion related reactions were reported as mild to moderate. Monitor patients for infusion-related reactions. Interrupt infusion for infusion reactions and institute appropriate medical management prior to continuing infusion at a slower rate.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).


Inform patients and their caregivers of the risk of developing infections during treatment with GAMIFANT, and to report any symptoms of infection [see WARNINGS AND PRECAUTIONS].


Advise patients and their caregivers that the patient should not receive live or live attenuated vaccines during GAMIFANT treatment [see WARNINGS AND PRECAUTIONS].

Infusion-Related Reactions

Advise patients and their caregivers of the potential for developing infusion-related reactions during treatment with GAMIFANT [see WARNINGS AND PRECAUTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No carcinogenicity or genotoxicity studies have been conducted with emapalumab-lzsg.

No studies have been conducted to evaluate the effects of emapalumab-lzsg on fertility; however, no adverse effects on male or female reproductive organs were observed in the 8- or 13-week repeat-dose toxicity studies in cynomolgus monkeys.

Use In Specific Populations


Risk Summary

There are no available data on GAMIFANT use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In an animal reproduction study, a murine surrogate anti-mouse IFNγ antibody administered to pregnant mice throughout gestation crossed the placental barrier, and no fetal harm was observed (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.


Animal Data

In a mouse embryo-fetal development study, a murine surrogate anti-mouse IFNγ antibody was administered every 3-4 days throughout organogenesis and late gestation at doses of 0, 30, 75 or 150 mg/kg/occasion. The surrogate antibody was detected in the plasma of all treated pregnant mice and their corresponding fetuses. No maternal toxicity occurred and there was no evidence of teratogenicity or effects on embryo-fetal survival or growth.


Risk Summary

There is no information regarding the presence of emapalumab-lzsg in human milk, the effects on the breastfed child, or the effects on milk production. Published data suggest that only limited amounts of therapeutic antibodies are found in breast milk and they do not enter the neonatal and infant circulations in substantial amounts.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GAMIFANT and any potential adverse effects on the breastfed child from GAMIFANT or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness of GAMIFANT have been established in pediatric patients, newborn and older, with primary HLH that is reactivated or refractory to conventional therapies. Use of GAMIFANT is supported by a single-arm trial in 27 pediatric patients with reactivated or refractory primary HLH. This study included pediatric patients in the following age groups: 5 patients newborn to 6 months, 10 patients 6 months to 2 years, and 12 patients from 2 years to 13 years [see Clinical Studies].

Geriatric Use

Clinical studies of GAMIFANT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Overdose & Contraindications


No Information provided



Clinical Pharmacology


Mechanism Of Action

Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.


IFNγ Inhibition

Emapalumab-lzsg reduces the plasma concentrations of CXCL9, a chemokine induced by IFNγ.

Cardiac Electrophysiology

At a dose of 3 mg/kg GAMIFANT does not prolong the QT interval to any clinically relevant extent.


The pharmacokinetics of emapalumab-lzsg were evaluated in healthy adult subjects and in patients with primary HLH.

Following a 1 mg/kg emapalumab-lzsg dose, median steady state peak concentration was 44 mcg/mL, which was 2.9 times higher than after the first dose. The median steady state trough concentration was 25 mcg/mL, which was 4.3 times higher than after the first dose. Emapalumab-lzsg AUC increases slightly more than proportionally between 1 and 3 mg/kg doses, and less than proportionally at 3, 6, and 10 mg/kg doses.

Emapalumab-lzsg exhibits target-mediated clearance dependent on IFNγ production, which can vary between and within patients as a function of time and can affect the recommended dosage [see DOSAGE AND ADMINISTRATION]. Emapalumab-lzsg steady state is achieved by the 7th infusion when the IFNγ production is moderate. At high IFNγ production, steady-state is reached earlier due to a shorter half-life.


The central and peripheral volumes of distribution in a subject with body weight of 70 kg are 4.2 and 5.6 L, respectively.


Emapalumab-lzsg elimination half-life is approximately 22 days in healthy subjects, and ranged from 2.5 to 18.9 days in HLH patients.

Emapalumab-lzsg clearance is approximately 0.007 L/h in healthy subjects.

In patients, the total clearance of emapalumab-lzsg was significantly influenced by the production of IFNγ, demonstrating target mediated clearance of emapalumab-lzsg.


The metabolic pathway of emapalumab-lzsg has not been characterized. Like other protein therapeutics, GAMIFANT is expected to be degraded into small peptides and amino acids via catabolic pathways.

Specific Populations

Body weight (2 to 82 kg) was a significant covariate of emapalumab-lzsg pharmacokinetics, supporting body weight-based dosing.

No clinically significant differences in the pharmacokinetics of emapalumab-lzsg were observed based on age (0.02 to 56 year), sex (53% Females), race (71.4% Caucasian, 12.2% Asian and 8.2% Black), renal impairment including dialysis, or hepatic impairment (mild, moderate, and severe).

Drug Interaction Studies

No drug-drug interaction studies have been conducted with GAMIFANT.

Clinical Studies

The efficacy of GAMIFANT was evaluated in a multicenter, open-label, single-arm trial NI-0501-04 (NCT01818492) in 27 pediatric patients with suspected or confirmed primary HLH with either refractory, recurrent, or progressive disease during conventional HLH therapy or who were intolerant of conventional HLH therapy.

Patients were required to fulfill the following criteria for enrollment: primary HLH based on a molecular diagnosis or family history consistent with primary HLH or five out of the 8 criteria fulfilled: fever, splenomegaly, cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin < 9 , 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 ≥ 2400 U/mL. Patients had to have evidence of active disease as assessed by treating physician. Patients had to fulfill one of the following criteria as assessed by the treating physician: having not responded or not achieved a satisfactory response or not maintained a satisfactory response to conventional HLH therapy, or intolerance to conventional HLH treatments. Patients with active infections caused by specific pathogens favored by IFNγ neutralization were excluded from the trial (e.g., mycobacteria and Histoplasma Capsulatum). Patients received prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infections.

Twenty-seven patients enrolled and received treatment in the study and twenty patients (74%) completed the study. Seven patients (26%) were prematurely withdrawn. Twenty-two patients (81%) enrolled onto the open-label extension study which monitored patients for up to 1 year after HSCT or after the last GAMIFANT infusion (NI-0501-05; NCT02069899).

The study treatment duration was up to 8 weeks after which patients could continue treatment on the extension study. All patients received an initial starting dose of GAMIFANT of 1 mg/kg every 3 days. Subsequent doses could be increased to a maximum of 10 mg/kg based on clinical and laboratory parameters interpreted as unsatisfactory response. Forty-four percent of patients remained at a dose of 1 mg/kg, 30% of patients increased to 3-4 mg/kg and 26% of patients increased to 6-10 mg/kg. The median time to dose increase was 27 days (range: 3-31 days) with 22% of patients requiring a dose increase in the first week of treatment.

All patients received dexamethasone as background HLH treatment with doses between 5 to 10 mg/m²/day. Cyclosporine A was continued if administered prior to screening. Patients receiving methotrexate and glucocorticoids administered intrathecally at baseline could continue these treatments.

In Study NI-0501-04, the median patient age was 1 year (0.2 to 13). Fifty-nine percent of the patients were female, 63% were Caucasian, 11% were Asian, and 11% were Black.

A genetic mutation known to cause HLH was present 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%).

The HLH mutations in the population enrolled are described in Table 3.

Table 3: HLH Mutations in Patients with Primary HLH with Prior Therapy

HLH Genetic Confirmation 22 (82)
FHL3 - UNC13D 7 (26)
FHL2 - PRF1 5 (19)
Griscelli Syndrome type 2 (RAB27A) 5 (19)
FHL5 - STXBP2 (UNC18B) 2 (7.4)
FHL4 - STX11 1 (3.7)
X-linked Lymphoproliferative Disorder 1 1 (3.7)
X-linked Lymphoproliferative Disorder 2 1 (3.7)

All patients received previous HLH treatments. Patients received a median of 3 prior agents before enrollment into the trial. Prior regimens included combinations of the following agents: dexamethasone, etoposide, cyclosporine A, and anti-thymocyte globulin.

At baseline entry into the study, 78% of patients had elevated ferritin levels, thrombocytopenia (70% with platelet count of < 100 x 109cells/L), hypertriglyceridemia (67%) with triglyceride level > 3 mmol/L. Central nervous system findings were present in 37% of patients. Forty-one percent of patients had active infections not due to specific pathogens favored by IFNγ neutralization at the time of GAMIFANT initiation.

The efficacy of GAMIFANT was based upon overall response rate (ORR) at the end of treatment, defined as achievement of either a complete or partial response or HLH improvement. ORR was evaluated using an algorithm that included the following objective clinical and laboratory parameters: fever, splenomegaly, central nervous system symptoms, complete blood count, fibrinogen and/or D-dimer, ferritin, and soluble CD25 (also referred to as soluble interleukin-2 receptor) levels. Complete response was 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). Partial response was defined as normalization of ≥ 3 HLH abnormalities. HLH improvement was defined as ≥ 3 HLH abnormalities improved by at least 50% from baseline.

Table 4: Overall Response Rate at End of Treatment

Overall Response Rate
N (%) 17 (63)
(95% CI) (0.42, 0.81)
p-value† 0.013
Overall Response by Category
Complete response, n (%) 7 (26)
Partial response 8 (30)
HLH improvement 2 (7.4)
†p-value based on Exact Binomial Test at a one-sided significance level of 2.5% comparing proportion of patients with overall response to hypothesized null hypothesis of 40%.
CI = confidence interval

The median duration of first response, defined as time from achievement of first response to loss of first response, is not reached (range: 4-56+ days). Seventy percent (19/27) of patients proceeded to HSCT.

Medication Guide


No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

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