Emapalumab-lzsg
Emapalumab-lzsg Uses, Dosage, Side Effects, Food Interaction and all others data.
Emapalumab-lzsg, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab-lzsg development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018. The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy. As well, emapalumab was given the status of PRIME by the EMA.
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. 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.
| Trade Name | Emapalumab-lzsg |
| Availability | Prescription only |
| Generic | Emapalumab |
| Emapalumab Other Names | Emapalumab, emapalumab-lzsg |
| Related Drugs | Gamifant |
| Type | Intravenous |
| Formula | C6430H9898N1718O2038S46 |
| Weight | 154400.0 Da |
| Protein binding | Monoclonal antibodies are usually not required to have protein binding studies. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Emapalumab-lzsg is an interferon gamma blocking antibody used to treat primary hemophagocytic lymphohistiocytosis.
Emapalumab-lzsg 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.
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. 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.
Emapalumab-lzsg is also used to associated treatment for these conditions: Progressive, refractory, primary intolerance with conventional therapy, recurrent Hemophagocytic Lymphohistiocytosis
How Emapalumab-lzsg works
Emapalumab-lzsg acts by binding and neutralizing interferon-gamma. 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. 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.
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.
Toxicity
There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.
Emapalumab-lzsg Disease Interaction
Volume of Distribution
The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.
Elimination Route
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.
Half Life
Emapalumab-lzsg elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.
Clearance
Emapalumab-lzsg 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.
Elimination Route
Emapalumab-lzsg presents a target-mediated clearance that is dependent on interferon-gamma production.
Innovators Monograph
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