Phase 2 Study Shows Promise for Targeted Therapy in Interferon Gamma–Driven Sepsis

Published on: January 7, 2026

A new Phase 2a clinical trial suggests that targeting specific immune pathways may improve outcomes for a high-risk subset of sepsis patients, with potential implications for future infection prevention and sepsis programs. Sobi announced topline results from the EMBRACE study on January 7, 2026, evaluating Gamifant for interferon gamma–driven sepsis, a newly described sepsis endotype associated with poor outcomes.

Sepsis remains a leading global cause of death, but growing evidence shows it is not a single disease entity. Recent research has identified distinct sepsis endotypes that may require different treatment approaches. Approximately 20 percent of patients fall into the interferon gamma–driven sepsis category, which is characterized by elevated CXCL9 and detectable interferon gamma levels and is associated with 28-day mortality rates exceeding 40 percent.

Major Sepsis Types and Endotypes

Sepsis is increasingly recognized as a heterogeneous syndrome rather than a single disease. Research over the past decade has identified multiple sepsis types and immune endotypes, each associated with different biological pathways and clinical outcomes.

Classic Sepsis
A life-threatening organ dysfunction caused by a dysregulated host response to infection. Traditionally treated with early antibiotics, source control, fluids, and supportive care.

Septic Shock
A severe subset of sepsis marked by profound circulatory, cellular, and metabolic abnormalities. Patients require vasopressors to maintain blood pressure and have a significantly higher mortality risk.

Hyperinflammatory Sepsis
Characterized by excessive immune activation and cytokine release. Patients may experience rapid organ dysfunction driven by overwhelming inflammation.

Immunoparalytic Sepsis
Marked by immune suppression following an initial inflammatory phase. Patients are vulnerable to secondary infections and poor pathogen clearance.

Interferon Gamma–Driven Sepsis (IDS)
A newly described endotype identified through biomarker profiling. IDS is characterized by elevated interferon gamma and CXCL9 levels and is associated with high mortality rates. This subgroup appears biologically distinct and may benefit from targeted immunomodulatory therapies.

Mixed or Transitional Endotypes
Some patients exhibit overlapping features or shift between inflammatory and immunosuppressed states during their illness, complicating treatment and prevention strategies.

Reference

van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity. 2021 Nov 9;54(11):2450-2464. doi: 10.1016/j.immuni.2021.10.012. PMID: 34758337.

The EMBRACE trial was a randomized, double-blind Phase 2a study conducted at 24 sites in Greece. It enrolled 75 patients with interferon gamma–driven sepsis and tested low- and high-dose emapalumab alongside standard of care compared with placebo. The primary endpoint was improvement in organ dysfunction, measured by changes in Sequential Organ Failure Assessment scores over 28 days.

Topline results showed proof of concept, with observed improvements in organ function and survival. For IPC teams, the findings highlight the growing role of precision medicine in sepsis care and reinforce the importance of early identification, biomarker awareness, and collaboration with clinical and antimicrobial stewardship teams. While emapalumab is not yet approved for sepsis, the results signal a potential shift toward targeted immunotherapies in managing severe infection syndromes.