Emapalumab, the very first drug for treatment of Primary Hemophagocytic Lymphohistiocytosis (HLH) approved for use in children

Reepa Agrawal
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Emapalumab, the very first drug for treatment of Primary Hemophagocytic Lymphohistiocytosis (HLH) approved for use in children 04 Jan, 2019

The first drug, Emapalumab for targeted treatment of Primary Hemophagocytic Lymphohistiocytosis (HLH) has been approved by the US FDA. This drug may help patients (pediatric including newborns as well as adults) with refractory, recurrent, progressive primary HLH and those refractory to HLH standard of care treatment to buy time till they can undergo hematopoietic stem cell transplant (HSCT). Till now this disease was being managed with chemotherapeutic agents and steroids, none specifically targeted its pathogenesis.

Emapalumab is produced by recombinant DNA technology in cells of ovaries of Chinese hamsters. It is a monoclonal antibody which specifically blocks and neutralises interferon gamma (IFN y). HLH is a rare condition which results due to cytokine storm, most important being interferon gamma. It can be primary (genetic defect) or secondary (triggered by any infection/ hyperinflammation). It is diagnosed by a constellation of biochemical findings in form of hypertriglyceridemia, raised ferritin, deranged liver function test and hematological findings such as cytopenias (mainly bicytopenia), hemophagocytes in bone marrow, positive d-dimer, coagulation abnormalities and clinical findings such as fever, hepatosplenomegaly.

Emapalumab was studied in a clinical trial which enrolled 27 pediatric primary HLH patients and its efficacy was proved as being statistically significant in terms of overall response rate. Also, 70 percent of patients could get a HSCT. Most common adverse events (more than 20%) reported were infections, infusion related reactions, hypertension and fever. Tuberculosis (TB) including latent TB needs to be ruled out before starting therapy with this drug. It is also important to give prophylaxis against herpes zoster, pneumocystis jiroveci and fungal infections when on treatment with emapalumab.

It is available as solution for injection in 10mg/2ml and 50mg/10ml single dose vial. It is to be administered through intravenous infusion over one hour twice per week until HSCT. This drug is manufactured by Novimmune SA, Switzerland and distributed by Sobi Inc, Waltham, MA under the brand Gamifant. In Europe emapalumab has been granted orphan designation and PRIority MEdicine (PRIME) status by the EMA (European Medicines Agency.



Source: US FDA. https://www.fda.gov/
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