Emapalumab-lzsg offers new hope for children and adults with severe hyperinflammation, marking a major breakthrough in targeted therapy for macrophage activation syndrome.
The US Food and Drug Administration has approved emapalumab-lzsg for the treatment of macrophage activation syndrome in adults and children with Still’s disease, including systemic juvenile idiopathic arthritis and adult-onset Still’s disease.
This is the first FDA-approved therapy for MAS, a life-threatening complication of Still’s disease.
The approval of the drug known commercially as Gamifant and made by global biopharma company Sobi, was based on pooled efficacy and safety data from the pivotal Phase 3 EMERALD trial and a multicentre study.
Results demonstrated that 54% (21/39) of patients treated with emapalumab-lzsg achieved a complete response at week eight, and 82% (32/39) reached clinical remission of MAS, defined by a visual analog scale (VAS) score of ≤1 cm.
“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 Dr Alexei A. Grom, professor of paediatrics and research director of rheumatology at Cincinnati Children’s Hospital.
“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.”
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Previously, treatment options for MAS have been limited primarily to high-intensity immunosuppression, often including glucocorticoids, cyclosporine, and biologics used off-label. The FDA’s approval of emapalumab-lzsg offers a targeted mechanism of action against interferon gamma (IFNγ), a key cytokine in the pathogenesis of HLH/MAS.
The monoclonal antibody binds and neutralises IFNγ, interrupting the cytokine cascade responsible for the hyperinflammatory state seen in HLH and MAS. It is already FDA-approved for primary HLH in paediatric and adult populations with disease refractory to conventional therapies.
The safety profile observed in the studies was consistent with prior experience, with the most frequent adverse events (≥20%) being viral infections, such as cytomegalovirus infection or reactivation, and rash. Importantly, no new safety signals were identified in this patient population.
“With our expertise in primary hemophagocytic lymphohistiocytosis, we understand the urgency of managing MAS quickly to improve patient outcomes,” said Guido Oelkers, Sobi’s chief executive officer.
“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”.
MAS is a form of secondary hemophagocytic lymphohistiocytosis (HLH), triggered by autoimmune or autoinflammatory diseases. Hallmark features include persistent high fever, cytopenias, hyperferritinemia, hepatosplenomegaly and coagulopathy. It is a medical emergency, and early recognition and targeted treatment are critical to reduce morbidity and mortality.
