{"id":"emapalumab-lzsg","rwe":[],"tags":[],"phase":"discontinued","safety":{"boxedWarnings":[],"drugInteractions":["7 DRUG INTERACTIONS 7.1 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."],"commonSideEffects":["6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions ( 5.1 )] Increased Risk of Infection with Use of Live Vaccines [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] In patients with primary HLH, the most common adverse reactions (≥ 20%) were: infections, hypertension, infusion-related reactions, and pyrexia. ( 6.1 ) In patients with HLH/MAS in Still’s disease, the most common adverse reactions (≥20%) were:viral infections, including cytomegalovirus infection or reactivation, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 1-866-773-5274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Primary HLH 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 ( 2.1 ) and Clinical Studies ( 14 )] . 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 4. Table 4 : Adverse Reactions Reported in 10% of Patients with Primary HLH Adverse Reactions GAMIFANT (%) (N = 34) Infections a 56 Hypertension b 41 Infusion-related reactions c 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 a Includes viral, bacterial, fungal, and infections in which no pathogen was identified b Includes secondary hypertension c Includes 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. HLH/MAS The safety of GAMIFANT was evaluated in two open-label clinical studies in patients with HLH/MAS in Stills disease, including sJIA [see Clinical Studies ( 14.2 )] . The pooled safety data from these two studies included 39 patients who received an initial dose of 6 mg/kg followed by 3 mg/kg every 3 days until Day 16, and then twice weekly thereafter. The median duration of treatment with GAMIFANT was 29 days (range: 7 to 220 days) and the median cumulative dose was 33 mg/kg (range: 12 to 175 mg/kg). 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. Pneumonia led to drug discontinuation in one patient (3%). The most common adverse reactions (≥20%) were viral infections, including cytomegalovirus in"],"contraindications":["4 CONTRAINDICATIONS None. None. ( 4 )"]},"status":"discontinued","trials":["NCT05744063","NCT06996119","NCT03985423","NCT05001737"],"aliases":["NI-0501"],"patents":[],"pricing":[],"offLabel":[],"timeline":[],"aiSummary":"","brandName":"Emapalumab-Lzsg","companyId":"swedish-orphan-biovitrum","ecosystem":[],"mechanism":{"target":"Interferon gamma","drugClass":"Interferon gamma Blocker [EPC]","explanation":"1 INDICATIONS AND USAGE 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. adult and pediatric ( newborn and older) patients with 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. GAMIFANT 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. ( 1 ) adult and pediatric (newborn and older) patients with 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. ( 1 )","oneSentence":"12.1 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."},"commercial":null,"references":[],"biosimilars":[],"companyName":"Swedish Orphan Biovitrum","competitors":[],"dataSources":[{"url":"https://clinicaltrials.gov","name":"ClinicalTrials.gov","fields":["trialDetails","trials"],"retrievedDate":"2026-04-07"},{"url":"https://drugcentral.org","name":"DrugCentral","fields":["indications","contraindications","safety","target","drugInteractions"],"retrievedDate":"2026-04-07"}],"genericName":"Emapalumab-Lzsg","indications":{"approved":[{"name":"Primary hemophagocytic lymphohistiocytosis","diseaseId":"primary-hemophagocytic-lymphohistiocytosis","approvalDate":"","lineOfTherapy":"","approvalCountry":"United States"}],"offLabel":[],"pipeline":[]},"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT05744063","phase":"Phase 4","title":"An Open Label, Single Arm, Multi-Centre, Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of Primary Hemophagocytic Lymphohistiocytosis in Treatment Experie","status":"COMPLETED","sponsor":"Swedish Orphan Biovitrum","isPivotal":false,"enrollment":13,"indication":"Primary Hemophagocytic Lymphohistiocytosis","completionDate":"2025-08-08"},{"nctId":"NCT06996119","phase":"Phase 1","title":"Pilot Study of Emapalumab With Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis for Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation","status":"NOT_YET_RECRUITING","sponsor":"City of Hope Medical Center","isPivotal":false,"enrollment":15,"indication":"Acute Myeloid Leukemia, Graft Versus Host Disease","completionDate":"2027-05-25"},{"nctId":"NCT03985423","phase":"Phase 2","title":"A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis","status":"TERMINATED","sponsor":"Swedish Orphan Biovitrum","isPivotal":true,"enrollment":7,"indication":"Hemophagocytic Lymphohistiocytoses","completionDate":"2021-06-29"},{"nctId":"NCT05001737","phase":"Phase 3","title":"A Two-cohort, Open-label, Single Arm, Multicenter Study to Evaluate Efficacy, Safety and Tolerability, PK and PD, of Emapalumab in Children and Adults With MAS in Still's Disease or With MAS in System","status":"COMPLETED","sponsor":"Swedish Orphan Biovitrum","isPivotal":true,"enrollment":33,"indication":"Macrophage Activation Syndrome, Secondary Hemophagocytic Lymphohistiocytosis","completionDate":"2025-06-04"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"INTRAVENOUS","dosage_text":"2 DOSAGE AND ADMINISTRATION For intravenous infusion only: Primary HLH recommended starting dosage: 1 mg/kg as an intravenous infusion over 1 hour twice per week. ( 2.1 ) HLH/MAS in Still’s disease recommended starting dose: 6 mg/kg, followed by 3 mg/kg every 3 days for 5 doses, then 3 mg/kg twice per week. Given as an intravenous infusion over 1 hour. ( 2.2 ) For both indications, the dose may be titrated up to a maximum of 10 mg/kg. ( 2.5 , 2.6 ) 2.1 Recommended Dosage for Primary Hemophagocytic Lymphohistiocytosis The recommended starting dose of GAMIFANT is 1 mg/kg given as a central or peripheral 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 ( 2.5 )] . 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. 2.2 Recommended Dosage for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome GAMIFANT is administered as a central or peripheral intravenous infusion over 1 hour according to the dosage schedule in Table 1. Doses may be increased based on clinical and laboratory criteria [see Dosage and Administration ( 2.6 )] . Discontinue GAMIFANT when a patient no longer requires therapy for the treatment of HLH/MAS. Table 1. GAMIFANT Dosage in Patients with HLH/MAS Treatment Day GAMIFANT Dosage Day 1 6 mg/kg Days 4 to 16 3 mg/kg every 3 days for 5 doses From Day 19 onward 3 mg/kg twice per week (i.e., every 3 to 4 days) 2.3 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 Herpes Zoster infection, adenovirus, EBV and CMV as clinically indicated. 2.4 Prophylaxis and Concomitant Medication Information Prophylaxis Consider prophylaxis for Herpes Zoster, Pneumocystis jirovecii , and for fungal infections prior to GAMIFANT administration. Concomitant Medications For primary HLH patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 mg/m 2 to 10 mg/m 2 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 ( 14 )]. 2.5 Dose Modification Based on Response for Primary Hemophagocytic Lymphohistiocytosis The GAMIFANT dose may be titrated up if disease response is unsatisfactory (see Table 2) [see Clinical Pharmacology ( 12.3 )] . After the patient's clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response. Table 2: Dose Titration Criteria Treatment Day GAMIFANT Dose Criteria for Dose Increase Day 1 Starting Dose of 1 mg/kg N/A From Day 4 onwards 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/mm 3 and no improvement to > 50,000/mm 3 If baseline > 50,000/mm 3 and less than 30% improvement If baseline > 100,000/mm 3 and decrease to < 100,000/mm 3 Neutrophil count If baseline < 500/mm 3 and no improvement to > 500/mm 3 If baseline > 500/mm 3 to 1,000/mm 3 and decrease to < 500/mm 3 If baseline 1,000/mm 3 to 1,500/mm 3 and decrease to < 1,000/mm 3 Ferritin (ng/mL) If baseline ≥3,000 ng/mL and < 20% decrease If baseline < 3,000 ng/mL and any increase to > "},"formularyStatus":[],"apiManufacturers":[],"developmentCodes":[],"ownershipHistory":[],"therapeuticAreas":["Immunology"],"biosimilarFilings":[],"firstApprovalDate":"","companionDiagnostics":[],"firstApprovalCountry":null,"genericManufacturerList":[],"modality":"Small molecule","enrichmentLevel":3,"visitCount":0,"trialStats":{"total":2,"withResults":2},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}