November 20, 2018
On November 20, 2018, the Food and Drug Administration approved emapalumab (GAMIFANT, Novimmune SA), a monoclonal antibody that binds and neutralizes interferon gamma, for adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.
Approval was based on a multicenter, open-label, single-arm trial NI-0501-04 (NCT01818492) in 27 pediatric 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.
FDA granted this application priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).