Sobi Launches Phase 2a Trial of Gamifant for Interferon-Gamma-Driven Sepsis
核心洞察
Sobi (搜索) has initiated the EMBRACE Phase 2a clinical trial to evaluate Gamifant (emapalumab) for treating interferon-gamma-driven sepsis (搜索) (IDS (搜索)), a newly identified endotype affecting approximately 20% of sepsis (搜索) patients with 40-43% mortality rate.
The double-blind, randomized controlled trial will enroll 75 patients across 24 sites in Greece, targeting patients with the IDS (搜索) endotype who do not exhibit sepsis (搜索)-induced immunoparalysis.
The study represents a precision medicine approach to sepsis (搜索) treatment, with primary endpoints measuring improvement in organ function and secondary endpoints including 28-day mortality and changes in inflammatory biomarkers.
Sobi (搜索), a specialized international biopharmaceutical company, announced today a new research collaboration to investigate Gamifant (emapalumab) as a potential treatment for interferon-gamma (IFNγ)-driven sepsis (搜索) (IDS (搜索)). The Phase 2a clinical trial, named EMBRACE, will be presented at the International Symposium on Intensive Care and Emergency Medicine (ISICEM) Congress by Professor Evangelos Giamarellos-Bourboulis from the Hellenic Institute for the Study of Sepsis.
The research initiative targets a newly identified sepsis (搜索) endotype characterized by elevated levels of the chemokine CXCL9 and detectable IFNγ. This endotype represents approximately 20 percent of sepsis patients and is associated with poor clinical outcomes, including a 28-day mortality rate of 40-43%.
Targeting a Specific Sepsis Subgroup
The EMBRACE study will focus specifically on patients with the IDS (搜索) endotype who do not exhibit sepsis (搜索)-induced immunoparalysis. Patients with low human leukocyte antigen DR (HLA-DR) expression on monocytes, which is characteristic of immunoparalysis, will be excluded from the current trial.
"The EMBRACE Phase 2a study will adopt a precision immunotherapy approach for the treatment of sepsis (搜索) driven by the IDS (搜索) endotype, a patient group currently having limited therapeutic choices," said Prof. Giamarellos-Bourboulis, principal investigator and sponsor of the study.
Lydia Abad-Franch, MD, Head of Research & Development and Medical Affairs and Chief Medical Officer at Sobi (搜索), emphasized the company's strategic focus: "We are committed to advancing science and study Gamifant (emapalumab) in indications with a high unmet need and where excessive interferon gamma production plays a key role in driving hyperinflammation."
Trial Design and Objectives
The EMBRACE study (NCT06694701) is designed as a double-blind, randomized controlled trial to be conducted at 24 sites in Greece. The trial received approval in March 2025, and the first trial sites have already been initiated with patient screening underway.
The study will enroll 75 patients divided into three arms: two groups receiving different doses of Gamifant (emapalumab) alongside standard-of-care treatment, and one group receiving placebo with standard-of-care.
The primary endpoint is a ≥1.4-point decrease in the Sequential Organ Failure Assessment (SOFA) score from baseline to the end of the 28-day treatment period. Secondary endpoints include:
- 28-day mortality
- Safety and pharmacokinetic profiles
- Changes in key inflammatory biomarkers (CRP, IL-6, ferritin, IFNγ, and CXCL9)
Scientific Rationale and Disease Burden
Sepsis (搜索) remains one of the leading causes of mortality globally. A recent large study published in eBioMedicine in 2024 identified different sepsis endotypes, suggesting that varying patient subgroups may require differentiated treatment strategies.
The IDS (搜索) endotype is particularly concerning due to its high mortality rate. By targeting the IFNγ pathway, which drives hyperinflammation in these patients, researchers hope to reduce mortality, improve organ function, and accelerate recovery.
About Gamifant
Gamifant (emapalumab) is an anti-interferon gamma monoclonal antibody that binds to and neutralizes IFNγ. It is currently approved in the United States for the treatment of primary hemophagocytic lymphohistiocytosis (搜索) (HLH (搜索)) in both adult and pediatric patients with refractory, recurrent, or progressive disease, or in those who cannot tolerate conventional HLH therapy.
Primary HLH (搜索) is a rare syndrome of hyperinflammation that typically manifests within the first year of life and can be rapidly fatal without proper diagnosis and treatment. The FDA approval was based on data from Phase 2/3 studies.
The drug is administered through intravenous infusion over one hour twice per week until hematopoietic stem cell transplantation (HSCT).
Implications for Sepsis Treatment
If successful, this research could represent a significant advancement in sepsis (搜索) treatment by demonstrating the efficacy of targeted immunotherapy for specific patient subgroups. The precision medicine approach being tested in the EMBRACE trial aligns with growing evidence that sepsis is not a homogeneous condition but rather comprises distinct endotypes with different underlying pathophysiologies.
The trial design will be presented at ISICEM as abstract number A173 (poster number P249) by the EMBRACE study group, which includes O. Konstantinidou, E. Olntasi, H. Florou, A. Reininger, and E. Giamarellos-Bourboulis.
The results of this trial could potentially open new treatment avenues for a subset of sepsis (搜索) patients who currently face limited therapeutic options and poor outcomes.