Summary of Clinical Use

Emapalumab initially received FDA orphan drug designation for the treatment of hemophagocytic lymphohistiocytosis (HLH). Link here to the FDA record for this designation. Phase 2/3 clinical trial NCT01818492 evaluated emapalumab (NI-0501) in children with primary HLH, and a long-term follow-up study of HLH patients who were given emapalumab in an earlier clinical trial is ongoing (see NCT02069899). In November 2018, the FDA granted full approval for emapalumab's use as a treament option for adult and pediatric (newborn and older) patients with refractory, recurrent or progressive primary HLH or who are intolerant to conventional HLH therapy. SARS-CoV-2 and COVID-19: Emapalumab has been entered in to clinical trials that aim to determine its ability to combat the exaggerated immune response that drives cytokine storm and leads to tissue damage in the lung and other organs in patients with severe COVID-19.

Mechanism Of Action and Pharmacodynamic Effects

Familial (primary) HLH is a life-threatening immune disorder characterised by excessive production of activated lymphocytes (T cells, natural killer cells, B cells and macrophages) and severely elevated cytokine production. This unchecked immune activation causes neurological problems, abnormalities of the heart, kidneys, and other organs and tissues, anemia, and clotting problems. To date anti-inflammatory drugs such as dexamethasone, methotrexate and cortisol (hydrocortisone) as well as cyclosporin A and etoposide have been used to reduce the number of immune cells in HLH patients. Anti-IFNγ therapy is being exploited for this indication, with the aim of providing more effective and less toxic treatments, as suggested by studies in animal models of HLH [3].

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT01818492	A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis	Phase 2/Phase 3 Interventional	NovImmune SA
NCT02069899	Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody	N/A Interventional	NovImmune SA
NCT04324021	Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection.	Phase 2/Phase 3 Interventional	Swedish Orphan Biovitrum

External links

For extended ADME data see the following: Drugs.com