InflaRx's Vilobelimab Shows Unexpected Efficacy Signals From Halted Phase 3 Pyoderma Gangrenosum Trial

InflaRx N.V. (IFRX) unveiled fresh post-hoc analyses from its discontinued Phase 3 investigation into Vilobelimab for pyoderma gangrenosum treatment, revealing encouraging secondary findings despite the trial’s early termination in May 2025. The discontinuation followed an Independent Data Monitoring Committee recommendation citing insufficient interim efficacy, yet comprehensive analysis of the complete dataset uncovered treatment signals that management contends merit renewed evaluation.

The Clinical Challenge and Unmet Need

Pyoderma gangrenosum represents a severe, ulcerative neutrophilic disorder affecting the skin with no FDA-sanctioned therapeutic options currently available. Patients endure chronic, painful wounds resistant to standard interventions, leaving a significant treatment gap in this rare disease space. InflaRx’s trial marked the first randomized, controlled efficacy study in this indication utilizing complete target ulcer closure across two consecutive patient assessments as the primary success criterion—a rigorous endpoint reflecting the disease’s refractory nature.

Trial Population and Endpoint Performance

The investigation enrolled 54 patients across its duration, with 30 completing the full six-month treatment course before the predetermined stopping rule triggered termination. The primary composite endpoint—complete target ulcer closure—did not achieve statistical significance when comparing Vilobelimab recipients against placebo-treated controls. However, secondary and exploratory analyses painted a markedly different picture of the investigational therapy’s potential.

Secondary Efficacy Signals Warrant Attention

The secondary outcome measures revealed substantial improvements favoring Vilobelimab treatment. Complete disease remission occurred in 20.8% of drug-treated patients relative to 5.6% in the placebo cohort—a near four-fold differential. Furthermore, 36.4% of Vilobelimab recipients achieved more than 50% reduction in their target ulcer volume, compared to 16.7% in the placebo-comparator arm, indicating the drug may address the underlying pathophysiology even if not meeting the stringent primary endpoint.

Patient-reported outcomes demonstrated similarly encouraging trends. Dermatology Life Quality Index scoring decreased 31.1% among treated patients, reflecting meaningful quality-of-life improvements, whereas the placebo group experienced a nominal increase in symptom burden. These findings suggest Vilobelimab may provide tangible clinical benefit despite primary endpoint challenges.

Safety Profile and Tolerability

The safety dataset demonstrated that Vilobelimab was generally well-tolerated across the study population. Adverse event profiles remained predominantly mild-to-moderate in severity, with no unexpected safety signals emerging during the investigation. This favorable safety posture maintains the drug’s therapeutic window for future development considerations.

Post-Hoc Analyses Strengthen the Case

Subsequent comprehensive statistical modeling provided additional supportive evidence. Mixed model repeated measures analysis documented statistically significant ulcer volume reductions from week 14 through week 26 favoring Vilobelimab-treated patients. Covariance analyses similarly demonstrated significant improvements in both ulcer volume and area metrics—suggesting that extended treatment duration may optimize clinical outcomes in this difficult-to-manage patient population.

External clinical observers expressed measured optimism regarding these findings, noting that although the predetermined primary endpoint was not achieved, the collective data substantiate the therapeutic hypothesis of C5a/C5aR pathway inhibition in pyoderma gangrenosum pathogenesis. This mechanism targeting remains scientifically justified despite the trial’s discontinuation.

InflaRx Clarifies Trial Discontinuation Rationale

The company underscored that early termination decisions were predicated on interim data from the initial 30 enrolled patients, which lacked sufficient early efficacy signals to support continuation at that checkpoint. The full-dataset post-hoc analyses conducted following study closure revealed a substantially more favorable treatment effect profile, providing retrospective evidence of Vilobelimab’s clinical activity that interim interim assessments had not captured.

Strategic Path Forward and Regulatory Engagement

InflaRx intends to engage FDA representatives to explore alternative primary endpoint frameworks for future development. The company signaled that ongoing pyoderma gangrenosum program advancement would likely necessitate partnering arrangements, as institutional resources remain concentrated on Izicopan (INF904), the company’s oral C5aR inhibitor in advanced development stages.

Vilobelimab, marketed under the trade name GOHIBIC, maintains Emergency Use Authorization status in the United States for hospitalized COVID-19 patients requiring mechanical ventilation or extracorporeal membrane oxygenation support. The European Union granted marketing authorization under exceptional circumstances for severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection.

Financial and Market Context

Revenue generation from GOHIBIC reached €39 thousand during the first half of 2025 from U.S. distribution channels, compared with €42 thousand in the corresponding prior-year period. IFRX has ranged between $0.71 and $2.77 annually, with pre-market trading activity showing the stock at $0.97, representing a 4.89% decline on news of these trial results.