FDA Grants Emapalumab-Izsg Priority Review for Macrophage Activation Syndrome

The FDA granted emapalumab-izsg (Gamifant) priority review for adult and pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in Still disease with an inadequate response or intolerance to glucocorticoids or with recurrent MAS. The agency assigned the potential therapeutic a Prescription Drug User Fee Act date of June 27, 2025.¹

"HLH/MAS in Still disease is a serious and potentially fatal complication where patients can experience intense hyperinflammation and even multiple organ failure," Lydia Abad-Franch, MD, MBA, head of R&D and chief medical officer at Sobi, said in a news release.¹

The biologic license application is based on results from a pooled analysis of 2 studies. Investigators reported that approximately 53% of 39 patients had a complete response at week 9, and 85% had a complete response at any time point. In the EMERALD (NCT05001737) study, investigators assessed emapalumab for children and adults. They investigated the efficacy, safety, and tolerability for 8 weeks as well as the pharmacokinetics, pharmacodynamics, quality of life, and immunogenicity for up to 1 year after the last dose of the drug. Patients were separated into 2 cohorts, including MAS in the context of systemic juvenile idiopathic arthritis (sJIA) and adult-onset still disease (AOSD), as well as in the context of systemic lupus erythematous.

The primary end point included the proportion of individuals with complete response at week 8 after the first administration of the drug, with secondary end points including time to first complete remission, proportion of individuals with overall response, and time to first overall response.^1,2

In the second study (NCT03311854), investigators assessed the safety, tolerability, and efficacy of emapalumab in sJIA for AOSD for patients with developing MAS that had an inadequate response to high-dose glucocorticoid treatment. The primary end points included incidence, severity, causality, and outcomes of adverse events; number of individuals who withdrew for safety reasons; number of individuals achieving remission at week 8; time to first MAS remission; and number of individuals who withdrew due to lack of efficacy.³

For glucocorticoid tapering, investigators found the weekly mean glucocorticoid doses were reduced by approximately 70.1% after 2 weeks of treatment, with 72% of patients tapering to a clinically meaningful dose of 1 mg/kg/day or less and to 0.5 mg/kg/day or less for 44%. For clinical MA remission, 82.1% achieved remission at any time, with a median time to clinical remission of 3.3 weeks. The survival rate was 94.9% at 8 weeks, according to the results. Furthermore, no new safety signals were identified.⁴

"There is no approved therapy for HLH/MAS today. Gamifant (emapalumab-Izsg) selectively neutralizes interferon gamma (IFN-γ), a key driver of hyperinflammation, and if approved, may also help reduce the need for high-dose glucocorticoids in these patients,” Abad-Franch said in the news release.¹

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REFERENCES

1. US FDA grants Priority Review to Sobi's supplemental Biologics License Application (sBLA) for Gamifant (emapalumab-lzsg). News release. Swedish Orphan Biovitrum. February 27, 2025. Accessed February 27, 2025. https://prnmedia.prnewswire.com/news-releases/us-fda-grants-priority-review-to-sobis-supplemental-biologics-licence-application-sbla-for-gamifant-emapalumab-lzsg-302387090.html

2. Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (EMERALD). ClinicalTrials.gov identification: NCT05001737. Updated October 15, 2024. Accessed February 27, 2025. https://clinicaltrials.gov/study/NCT05001737

3. 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 identification: NCT03311854. Updated May 17, 2022. Accessed February 27, 2025. https://www.clinicaltrials.gov/study/NCT03311854

4. New data for emapalumab in the treatment of macrophage activation syndrome to be presented at the ACR conference. News release. Swedish Orphan Biovitrum. October 30, 2024. February 27, 2025. https://www.sobi.com/en/press-releases/new-data-emapalumab-treatment-macrophage-activation-syndrome-be-presented-acr-conference-2275523