Swedish biopharma company Sobi’s Gamifant (emapalumab-lzsg) is now FDA-approved to treat hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) in both children and adults with Still’s disease — including systemic juvenile idiopathic arthritis and adult-onset Still’s disease.
The approval — which is the first for treating MAS in the context of Still’s disease — covers patients who are unresponsive to or cannot tolerate glucocorticoids, or who have recurrent MAS.
Before Gamifant, the treatment of MAS in Still’s disease relied on high-dose corticosteroids, with biologic agents like anakinra or cyclosporine added off-label in severe or refractory cases.
What Is Still’s Disease?
Still’s disease is a rare systemic inflammatory condition seen in both children and adults. In pediatric cases, it’s known as systemic juvenile idiopathic arthritis, while in individuals over 16, it is referred to as adult-onset Still’s disease.
Symptoms often include daily high fevers, joint pain, a salmon-pink rash and elevated markers of inflammation in the blood. The disease is uncommon, with an estimated annual incidence of 0.1 to 0.4 cases per 100,000 people in Europe, with similar rates likely in the US.
What Is Macrophage Activation Syndrome (MAS)?
MAS is a severe and potentially life-threatening complication of Still’s disease. It may affect up to 23% of adults with Still’s disease.
It is considered a secondary form of HLH, and results from an overactive immune response, particularly driven by the protein interferon gamma.
MAS symptoms can include unrelenting high fever, low blood cell counts (cytopenias), abnormal blood clotting, liver dysfunction and enlargement of the liver and spleen. In some cases, it can rapidly lead to organ failure.
Retrospective studies suggest that MAS may occur clinically in around 10% of patients with the pediatric form of Still’s disease, with subclinical cases — where symptoms may be less apparent — affecting an additional 30% to 40%. Reported mortality rates for MAS range from 8% to 22% in children and up to 40% in adults, according to recent literature.
What Is Gamifant (Emapalumab)?
Gamifant is a monoclonal antibody that targets and neutralizes interferon gamma (IFNγ), helping to reduce the excessive immune activity associated with MAS.
Studies have shown that immune overactivation in MAS may involve excessive IFNγ, which triggers a cascade of inflammatory signaling that activates macrophages. These, in turn, release additional cytokines like IL-1β, IL-6, IL-18 and TNF-α — amplifying the response in a self-sustaining loop that can worsen tissue damage.
Research has also identified biomarkers such as CXCL9 and IL-18 that may help track disease activity in MAS, particularly in relation to IFNγ-driven inflammation.
Gamifant is given through intravenous infusion (IV) and is already approved in the US for treating primary HLH. This latest approval extends its use to a broader patient group affected by MAS in Still’s disease.
What Did the FDA Approval Involve?
The FDA based its decision on data pooled from two clinical studies — EMERALD and NI-0501-06 — which included 39 patients. At eight weeks, 54% (21 of 39) of patients achieved a complete response, and 82% (32 of 39) reached clinical MAS remission based on a visual assessment scale. Safety findings were in line with prior studies, with the most common side effects being viral infections — including reactivation of cytomegalovirus — and skin rash.
No new safety issues were identified, but the prescribing information includes warnings related to infection risk, given the drug’s immune-modulating effects.
Sobi did not provide additional details regarding launch timing or future development plans in the announcement. With this approval, Gamifant could offer a new targeted option for managing this critical complication.
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