Vilobelimab's Hidden Promise: InflaRx's Phase 3 Study Reveals Efficacy Signals Despite Primary Endpoint Miss

InflaRx N.V. (IFRX) disclosed comprehensive findings from its terminated Phase 3 trial evaluating Vilobelimab for pyoderma gangrenosum treatment, uncovering encouraging efficacy signals that the company argues justify deeper investigation. The study was halted in May 2025 following an Independent Data Monitoring Committee recommendation to discontinue due to futility, but subsequent full-dataset post-hoc analyses have emerged with more nuanced results than initial interim data suggested.

The Disease Challenge and Trial Design

Pyoderma gangrenosum represents a rare, ulcerative skin condition driven by neutrophilic inflammation that currently lacks FDA-approved therapeutic options. Patients endure severe, non-healing ulcers with limited treatment avenues available. InflaRx’s Phase 3 investigation marked the first randomized, placebo-controlled assessment in this indication to employ complete target ulcer closure across two consecutive visits as the primary outcome measure. The trial enrolled 54 patients total, with 30 advancing through the full six-month treatment course.

Secondary Endpoints Suggest Clinical Benefit

While the primary efficacy endpoint failed to demonstrate statistical significance between Vilobelimab and placebo, secondary measurements painted a different picture. Complete disease remission occurred in 20.8% of Vilobelimab recipients versus 5.6% receiving placebo—nearly four times the remission rate. On target ulcer volume reduction exceeding 50%, Vilobelimab achieved 36.4% response compared to 16.7% in controls. Quality-of-life assessments strengthened the signal, with Dermatology Life Quality Index scores declining 31.1% under active treatment while the placebo group experienced a minimal increase, indicating meaningful symptomatic improvement.

Mechanistic Evidence and Tolerability

Post-hoc analyses employing mixed model repeated measures methodology detected significant ulcer volume reductions favoring Vilobelimab from week 14 through week 26. Covariance analysis further confirmed statistically significant enhancements in both ulcer volume and area parameters. These patterns imply that extended treatment windows could produce superior clinical outcomes in this difficult-to-manage patient cohort. The C5a/C5aR inflammatory pathway targeting demonstrated an acceptable safety profile, with Vilobelimab demonstrating good tolerability and predominantly mild-to-moderate adverse events.

Strategic Path Forward and Market Context

InflaRx intends to engage with the FDA regarding potential alternative endpoint designs for future development. The company acknowledged that early termination relied upon preliminary 30-patient data lacking sufficient efficacy demonstrations at that juncture. Expanded analyses following trial closure provided enhanced clarity on Vilobelimab’s therapeutic potential. Further pyoderma gangrenosum advancement will likely proceed through partnership arrangements, as InflaRx prioritizes its oral C5aR inhibitor Izicopan’s (INF904) development pipeline.

Notably, Vilobelimab—known commercially as GOHIBIC—maintains Emergency Use Authorization status in the United States for hospitalized COVID-19 patients requiring invasive mechanical ventilation or extracorporeal membrane oxygenation support, with European Union exceptional circumstance authorization for acute respiratory distress syndrome. First-half 2025 GOHIBIC U.S. revenues reached €39 thousand compared to €42 thousand year-over-year.

IFRX stock has fluctuated between $0.71 and $2.77 annually and currently trades in premarket sessions at $0.97, reflecting a 4.89% decline.