BACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome 
characterized by immune dysregulation and hyperinflammation. It typically 
manifests in infancy and is associated with high mortality.
METHODS: We investigated the efficacy and safety of emapalumab (a human 
anti-interferon-γ antibody), administered with dexamethasone, in an open-label, 
single-group, phase 2-3 study involving patients who had received conventional 
therapy before enrollment (previously treated patients) and previously untreated 
patients who were 18 years of age or younger and had primary hemophagocytic 
lymphohistiocytosis. The patients could enter a long-term follow-up study until 
1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year 
after the last dose of emapalumab, if transplantation was not performed. The 
planned 8-week treatment period could be shortened or extended if needed 
according to the timing of transplantation. The primary efficacy end point was 
the overall response, which was assessed in the previously treated patients 
according to objective clinical and laboratory criteria.
RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 
previously treated patients and 7 previously untreated patients) had received 
emapalumab; 26 patients completed the study. A total of 63% of the previously 
treated patients and 65% of the patients who received an emapalumab infusion had 
a response; these percentages were significantly higher than the prespecified 
null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously 
treated group, 70% of the patients were able to proceed to transplantation, as 
were 65% of the patients who received emapalumab. At the last observation, 74% 
of the previously treated patients and 71% of the patients who received 
emapalumab were alive. Emapalumab was not associated with any organ toxicity. 
Severe infections developed in 10 patients during emapalumab treatment. 
Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis.
CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with 
primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the 
European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, 
NCT01818492 and NCT02069899.).