Key Takeaways
- First FDA-Approved Macrophage Activation Syndrome (MAS) Therapy: Gamifant is now the first and only FDA-approved treatment for hemophagocytic lymphohistiocytosis/MAS in patients with Still’s disease, including systemic juvenile idiopathic arthritis and adult-onset Still’s disease.
- Strong Clinical Response: In pooled trial data, 54% of patients achieved a complete response and 82% achieved clinical remission by week eight, supporting Gamifant’s efficacy in both adults and children.
- Steroid-Sparing Option: Gamifant offers a new therapeutic alternative for patients with inadequate response or intolerance to glucocorticoids, addressing a major unmet need in hyperinflammatory disease management.
The FDA has approved Sobi’s Gamifant (emapalumab-lzsg) as the first-ever treatment for both adult and pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in the context of known or suspected Still's disease, including systemic juvenile idiopathic arthritis (sJIA). The therapy is indicated for those who have shown an inadequate response or intolerance to glucocorticoids or experiencing recurrent MAS. Approval was based on results from the Phase III EMERALD (NCT05001737) and NI-0501-06 (NCT03311854) trials.1
What Clinical Evidence Supported the FDA’s Decision to Approve Gamifant for MAS in Still’s Disease?
"With our expertise in primary hemophagocytic lymphohistiocytosis, we understand the urgency of managing MAS quickly to improve patient outcomes," said Guido Oelkers, CEO, Sobi, in a press release. "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."
Key Findings from the EMERALD Trial
- The two-cohort, open-label, single-arm, multicenter EMERALD trial evaluated the safety, tolerability, and efficacy of Gamifant in 33 adult and pediatric patients with HLH/MAS in Still's disease or HLH/MAS in systemic lupus erythematosus (SLE), presenting with an inadequate response to high-dose glucocorticoid treatment.
- Cohort 1 was defined as MAS in the context of sJIA and adult-onset Still's disease (AOSD), while cohort 2 was defined as MAS in the context of pediatric and adult SLE.
- The primary endpoint of the trial was complete remission (CR) at week eight after first administration.
- Key secondary endpoints included, but were not limited to, time to first complete remission, proportion of subjects with overall response (defined by complete or partial remission), MAS recurrence at any time after achieving CR, and the evolution of laboratory parameters.2
Insights From the NI-0501-06 Pilot Trial
- The pilot, open-label, single-arm, multicenter NI-0501-06 trial evaluated the safety, tolerability, pharmacokinetics, and efficacy or intravenous administrations of Gamifant in 14 patients with sJIA or AOSD developing MAS/HLH.
- Primary endpoints included, but were not limited to, the incidence, severity, causality, and outcomes of adverse events (AEs); the number of patients withdrawn due to safety reasons; time to first MAS remission; and survival time.3
Efficacy and Safety Summary
- Results from a pooled analysis of the trials showed that 54% of patients achieved a complete response and 82% achieved CR by week eight.
- The safety profile of Gamifant was reported to be consistent with previous trials. Common AEs, which were reported in less than 20% of patients, included viral infections and rash.1
Epidemiological Context
According to Medscape, MAS is most common in children with sJLA, however, the incidence in the United States is currently unknown. Onset of the disease is most common around 14 years of age.4 According to Orphanet, the prevalence of AOSD is one out of every 100,000 people, with women having a slightly higher chance of getting infected. However, the exact incidence is difficult to determine due to its broad, non-specific clinical presentation.
"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, pediatrics, research director division of rheumatology, Cincinnati Children's Hospital Medical Center, in the press release. "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."
References
FDA approves Gamifant® (emapalumab-lzsg) as first-ever treatment for adults and children with Macrophage Activation Syndrome in Still's disease. PR Newswire. June 28, 2025. Accessed June 30, 2025. https://prnmedia.prnewswire.com/news-releases/fda-approves-gamifant-emapalumab-lzsg-as-first-ever-treatment-for-adults-and-children-with-macrophage-activation-syndrome-in-stills-disease-302493713.html
Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (EMERALD). Clinicaltrials.gov. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05001737
A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH). Clinicaltrials.gov. Accessed June 30, 2025. https://www.clinicaltrials.gov/study/NCT03311854
Macrophage Activation Syndrome. Medscape. Accessed June 30, 2025. https://emedicine.medscape.com/article/1380671-overview#a6
Adult-onset Still disease. Orphanet. Accessed June 30, 2025. https://www.orpha.net/en/disease/detail/829
