FDA Approves Emapalumab-Lzsg: First Treatment for Macrophage Activation Syndrome

On June 28, 2025, the U.S. Food and Drug Administration (FDA) announced its approval of emapalumab-lzsg (brand name Gamifant), marking a significant advancement as the first-ever treatment specifically for macrophage activation syndrome (MAS) associated with Still disease. This approval provides a new therapeutic avenue for patients suffering from this rare but severe condition, which can lead to life-threatening complications due to hyperinflammation.

The approval follows extensive clinical trials, including the phase 3 EMERALD trial (NCT05001737) and NI-0501-06 (NCT03311854), which evaluated the efficacy and safety of emapalumab in patients experiencing MAS symptoms. According to data published by Sobi, the manufacturer of emapalumab, 54% of trial participants achieved a complete response at week 8, while 82% experienced clinical remission. This underscores the drug's potential to significantly improve patient outcomes where conventional glucocorticoid therapies have failed.

"MAS in Still disease is characterized by severe hyperinflammation and can lead to multi-organ failure. The introduction of emapalumab represents a crucial development for both adult and pediatric patients who have limited options available to them," stated Dr. Alexei A. Grom, Professor of Pediatrics and Research Director at Cincinnati Children’s Hospital Medical Center. His insights reflect the urgent need for effective treatments for this debilitating condition.

Macrophage activation syndrome is a serious complication often associated with various rheumatic diseases, particularly Still disease. It is distinguished by symptoms such as persistent high fever, elevated ferritin levels, coagulopathies, and cytopenia. In some cases, MAS can escalate into multi-organ failure or even death if not managed effectively. Emapalumab, a monoclonal antibody that targets and neutralizes interferon gamma, aims to alleviate such hyperinflammation, thus attenuating the reliance on high-dose glucocorticoids that have been traditionally used.

The FDA's decision to approve emapalumab-lzsg came after the drug was previously granted a priority review status, expediting its evaluation as a promising treatment alternative. This expedited process highlights the urgent medical needs that exist for patients with MAS in Still disease, where the lack of effective treatments has been a critical concern for healthcare providers.

"With our experience in primary hemophagocytic lymphohistiocytosis (HLH), we recognize the importance of promptly addressing MAS to enhance patient outcomes," remarked Guido Oelkers, CEO of Sobi. He emphasized that emapalumab has already demonstrated meaningful efficacy in treating primary HLH, and its approval for MAS offers a new beacon of hope for affected patients.

Emapalumab is administered through intravenous infusion over a one-hour period. Pharmacists play a vital role in the treatment regimen, managing dosing, monitoring infusion processes, and addressing any potential adverse events. The most commonly reported side effects have included viral infections, consistent with previous studies on the drug.

The implications of this approval extend beyond individual patient care; they signify a notable advancement in the management of autoimmune conditions that have long been underserved in the realm of pharmacological intervention. As the medical community continues to grapple with the complexities of MAS and its association with Still disease, emapalumab-lzsg stands as a milestone that may reshape treatment protocols and improve quality of life for many patients.

The landscape of treatment for macrophage activation syndrome is evolving, with emapalumab paving the way for future innovations in therapeutic approaches. Researchers and clinicians alike remain hopeful that ongoing studies will further elucidate the long-term effects and potential additional applications of this groundbreaking treatment.