The U.S. Food and Drug Administration has approved Gamifant (emapalumab-lzsg) as the first-ever treatment for adult and pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in known or suspected Still's disease, including systemic Juvenile Idiopathic Arthritis (sJIA). The approval covers patients with inadequate response or intolerance to glucocorticoids, or those experiencing recurrent MAS.
Clinical Trial Results Drive Approval
The FDA approval is based on pooled data from two pivotal studies: the Phase 3 EMERALD study (NCT05001737) and NI-0501-06 (NCT03311854). In these trials, 54% (21/39) of patients achieved complete response at Week 8, while 82% (32/39) reached clinical MAS remission (VAS ≤1 cm) at Week 8.
"MAS in Still's disease is a serious and potentially life-threatening complication, marked by severe hyperinflammation and, in some cases, multi-organ failure," said Alexei A. Grom, MD, Professor of Pediatrics and Research Director Division of Rheumatology at Cincinnati Children's Hospital Medical Center. "Many patients affected by MAS—both young children and adults—face significant unmet medical needs. With Gamifant now as the first FDA-approved treatment for MAS, we have a new therapeutic option that helps control hyperinflammation and reduce our reliance on high-dose glucocorticoids."
Safety Profile and Administration
Safety and tolerability data were consistent with previous clinical studies of Gamifant. In patients with HLH/MAS in Still's disease, the most common adverse events (≥20%) were viral infections, including cytomegalovirus infection or reactivation, and rash. The drug is administered through intravenous infusion over one hour.
Understanding MAS and Its Clinical Impact
Macrophage activation syndrome is a severe complication of rheumatic diseases, occurring most frequently in Still's disease including systemic juvenile idiopathic arthritis and adult-onset Still's disease. MAS is characterized by fever, hepatosplenomegaly, liver dysfunction, cytopenias, coagulation abnormalities and hyperferritinaemia, potentially progressing to multiple organ failure and death.
HLH/MAS is a rare systemic disorder driven by interferon gamma (IFNγ) hyperinflammation, with common clinical manifestations including high persistent fever, elevated ferritin, cytopenias, coagulopathies, and hepatosplenomegaly. MAS is classified as a secondary form of haemophagocytic lymphohistiocytosis.
Mechanism of Action
Gamifant is an interferon gamma (IFNγ)-blocking monoclonal antibody that works by binding to and neutralizing IFNγ. When IFNγ is secreted in an uncontrolled manner, hyperinflammation occurs within the body. This targeted approach addresses the underlying pathophysiology of MAS.
Expanded Treatment Options
Prior to this approval, Gamifant was already the first and only FDA-approved treatment for adult and pediatric patients with primary HLH with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy. This new indication significantly expands treatment options for patients with secondary forms of HLH.
"With our expertise in primary hemophagocytic lymphohistiocytosis, we understand the urgency of managing MAS quickly to improve patient outcomes," said Guido Oelkers, Chief Executive Officer at Sobi. "Gamifant is already an established therapy making a meaningful difference for patients with primary HLH, and with this approval, we are excited about the opportunity to positively impact patients affected by MAS in Still's Disease."
The approval represents a significant advancement in treating this rare but serious condition, providing clinicians with a targeted therapeutic option for managing hyperinflammation in patients who have not responded adequately to conventional treatments.
