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| Primary information |
|---|
| ID | 15585 |
| Therapeutic ID | Th1610 |
| Protein Name | Emapalumab |
| Sequence | >Th1610_Emapalumab
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 154400 |
| Chemical Formula | C6430H9898N1718O2038S46 |
| Isoelectric Point | 6.6 - 7.2 |
| Hydrophobicity | NA |
| Melting point | 78 ºC |
| Half-life | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] |
| Description | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] |
| Indication/Disease | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] |
| Pharmacodynamics | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] |
| Mechanism of Action | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] |
| Toxicity | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] |
| Metabolism | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] |
| Absorption | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] |
| The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] |
| Clearance | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] |
| Categories | Antibodies |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon gamma |
| Brand Name | Gamifant |
| Company | NovImmune SA |
| Brand Description | NovImmune SA |
| Prescribed For | Intravenous |
| Chemical Name | 10 mg/2mL |
| Formulation | None. |
| Physical Appearance | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing |
| Route of Administration | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... |
| Recommended Dosage | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | 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. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |