FDA Approves Emapalumab for Haemophagocytic Lymphohistiocytosis

Approval is based on results from the NI-0501-04 trial

On 20 November 2018, the US Food and Drug Administration (FDA) approved emapalumab (GAMIFANT, Novimmune SA), a monoclonal antibody that binds and neutralises interferon gamma, for adult and paediatric (newborn and older) patients with primary haemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. 

Approval was based on a multicentre, open-label, single-arm trial NI-0501-04 (NCT01818492) in 27 paediatric patients with suspected or confirmed primary HLH with either refractory, recurrent, or progressive disease during conventional HLH therapy or who were intolerant of conventional HLH therapy.

All patients received an initial starting emapalumab dose of 1 mg/kg every 3 days. All patients received dexamethasone as background HLH treatment with doses between 5 to 10 mg/m2/day. Patients received prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infections prior to emapalumab administration. 

The overall response rate at the end of treatment, defined as achievement of either a complete or partial response or HLH improvement, was 63% (95% CI: 0.42, 0.81; p = 0.013). There were 7 complete and 8 partial responses, and 2 patients had HLH improvement, defined as ≥ 3 HLH abnormalities improved by at least 50% from baseline.

The most common adverse reactions occurring in ≥ 20% of patients were infections, hypertension, infusion-related reactions, and pyrexia.  

The recommended starting emapalumab dose is 1 mg/kg as an intravenous infusion over 1 hour twice per week. Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria. 

Full prescribing information for GAMIFANT is available here

FDA granted this application priority review, breakthrough therapy designation and orphan product designation. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.