Vilobelimab Shows Mixed Results in Pyoderma Gangrenosum Trial: Post-Hoc Data Reveals Efficacy Signals Despite Primary Endpoint Miss

InflaRx N.V. (IFRX) unveiled detailed findings from its terminated Phase 3 investigation of Vilobelimab for pyoderma gangrenosum, a rare and debilitating skin condition characterized by severe, non-healing ulcers. The trial was halted in May 2025 following recommendations from an Independent Data Monitoring Committee (IDMC), yet subsequent comprehensive re-analysis of the complete dataset has uncovered promising treatment signals that management believes merit continued exploration.

The Unmet Need in Rare Dermatology

Pyoderma gangrenosum presents a significant clinical challenge, as no FDA-approved therapeutic options currently exist for this neutrophilic ulcerative disorder. Patients endure painful, persistent lesions with limited treatment alternatives, creating urgent demand for novel interventions. InflaRx’s trial marked the first randomized, placebo-controlled investigation in this disease to employ complete target ulcer closure across consecutive visits as the primary efficacy measure—a rigorous benchmark reflecting real-world healing outcomes.

Trial Design and Initial Discontinuation

The study enrolled 54 patients, with 30 achieving the six-month treatment milestone. The primary endpoint failed to demonstrate statistical significance between Vilobelimab and placebo cohorts at the interim analysis stage, triggering the committee’s futility recommendation. However, this preliminary assessment did not capture the full therapeutic signal evident in the expanded dataset.

Secondary Endpoints Suggest Clinical Benefit

When examining measures beyond the primary endpoint, differentiation between treatment arms became apparent. Among Vilobelimab recipients, 20.8% attained complete disease remission compared to 5.6% in the placebo group—a three-fold difference. Substantial ulcer volume reduction exceeding 50% was achieved by 36.4% of treated patients versus 16.7% on placebo, representing meaningful clinical improvement. Quality-of-life assessments demonstrated notable distinctions as well: Dermatology Life Quality Index scores declined 31.1% in the Vilobelimab arm while increasing marginally in controls, indicating tangible patient-reported benefit.

Safety Profile Remains Favorable

Tolerability data supported continued investigation, with adverse events predominantly classified as mild to moderate intensity. No unexpected safety signals emerged, positioning Vilobelimab as a manageable therapeutic candidate for this chronically ill population.

Post-Hoc Analyses Strengthen the Case

Retrospective statistical modeling revealed statistically significant reductions in ulcer volume trajectory from weeks 14 through 26 favoring Vilobelimab. Covariance analyses further corroborated improvements in both ulcer volume and area measurements. These findings suggest that extended treatment duration may unlock greater therapeutic potential, particularly for this difficult-to-treat patient subset—a nuance potentially obscured by the shortened interim evaluation period.

Path Forward and Strategic Considerations

InflaRx leadership emphasized that early termination decisions relied on preliminary data from 30 patients, which lacked sufficient efficacy signals at that interim checkpoint. The expanded post-trial analysis provided considerably sharper visibility into Vilobelimab’s actual therapeutic window. The company intends to engage FDA stakeholders regarding alternative primary endpoints that may better capture treatment effect in pyoderma gangrenosum.

Given InflaRx’s strategic prioritization of its oral C5aR inhibitor Izicopan (INF904), future pyoderma gangrenosum development will likely proceed through partnership models. Both Vilobelimab and the broader C5a/C5aR pathway blockade rationale continue attracting external scientific interest despite the primary endpoint miss.

Current Market Position

Vilobelimab remains accessible in the United States via Emergency Use Authorization for hospitalized COVID-19 patients requiring mechanical ventilation or extracorporeal membrane oxygenation support. European regulatory approval has also been granted under exceptional circumstances for acute respiratory distress syndrome associated with SARS-CoV-2. Revenue from U.S. GOHIBIC (Vilobelimab’s commercial name) sales totaled €39 thousand during the first half of 2025, compared to €42 thousand in the corresponding year-ago interval.

IFRX equity has oscillated between $0.71 and $2.77 throughout the preceding twelve months. Current pre-market trading reflects $0.97 per share, representing a 4.89% decline from recent levels. Market sentiment remains cautious as investors await FDA discussions regarding alternative endpoints and potential partnership announcements.