While the Phase 3 trial of vilobelimab in ulcerative pyoderma gangrenosum (PG) was terminated earlier this year due to futility regarding its prespecified primary endpoint (as previously disclosed), subsequent post-hoc analyses suggest a positive trend in favor of vilobelimab, with signals indicating a potentially consistent treatment effect
InflaRx anticipates meeting with the FDA to determine a potential development path forward in PG, which the Company anticipates would only be conducted in collaboration with a partner
Dec. 30, 2025 -- InflaRx N.V. (Nasdaq: IFRX), a biopharmaceutical company pioneering anti-inflammatory therapeutics by targeting the complement system, today outlined multiple data analyses of the Phase 3 study for vilobelimab in pyoderma gangrenosum (PG), which was terminated earlier this year after an Independent Data Monitoring Committee (IDMC) recommended the trial be stopped early due to futility. The analyses disclosed today include the primary intent-to-treat analysis and several post-hoc analyses on the 54 patients enrolled in the trial at the time of study termination.
Prof. Niels C. Riedemann, Chief Executive Officer and Founder of InflaRx, said: “Our Phase 3 study was the first randomized placebo-controlled study in pyoderma gangrenosum using complete target ulcer closure on two consecutive visits as a stringent primary clinical endpoint, which has not been tested before in this rare disease. Our in-depth data analysis reveals signals of efficacy, particularly regarding ulcer volume reduction, which further supports the potential role of the C5a/C5aR pathway in certain neutrophilic skin diseases, such as PG. Depending on the outcome of our anticipated FDA interactions, our results may provide an opportunity to advance development in collaboration with a partner, which we may pursue in the future.”
The Phase 3 study had recruited a total of 54 patients at the time the interim analysis was conducted, including 30 patients who had completed 6 months of treatment. The primary clinical endpoint of complete target ulcer closure on two consecutive visits showed a difference in favor of vilobelimab over placebo of 20.8% versus 16.7% (p=NS (not significant)). Key secondary endpoints such as complete disease remission (complete closure of all ulcers) showed improvement in favor of vilobelimab over placebo (20.8% versus 5.6%, p=NS) and those with >50% reduction of target ulcer volume at week 26 (36.4% versus 16.7%, p=NS). In addition, patients reported feeling better as measured by the Dermatology Life Quality Index (DLQI) mean percentage change at the end of treatment visit (-31.1% versus 3.4%). Overall, vilobelimab was well tolerated. Observed treatment-emergent adverse events (TEAEs) were mostly mild to moderate, and patients with serious related on-treatment TEAEs were similarly distributed (6.3% in vilobelimab arm and 4.5% in placebo arm).
In addition, further post-hoc analyses showed that there is an overall treatment effect with vilobelimab when compared to placebo. These include an MMRM (mixed model repeated measures) for percent change in target ulcer volume, which showed an average effect over all visits in favor of vilobelimab over placebo (-45.4%, p=0.0428, Weeks 2 – 26 overall) when imputing patients with treatment-related discontinuation reasons, including patient level stopping criteria (PLSC) with a last observation carried forward (LOCF) approach. This analysis yielded a significant treatment difference for every week from Week 14 (-57.6%, p=0.0357) to Week 26 (-63.2%, p=0.0122) for vilobelimab over placebo.
In addition, ANCOVAs (analyses of covariance) for mean of percentage changes from baseline in volume and area from Week 12 until Week 26 were also in favor of vilobelimab, including mean of percentage change from baseline in volume (p=0.0111) and area (p=0.0072). These analyses suggest that treatment longer than 26 weeks with vilobelimab may provide improved treatment outcomes in this difficult-to-treat ulcerative PG population.
Alex G. Ortega Loayza, MD, MCR, CWSP, Professor and Interim Chair, Department of Dermatology, Oregon Health and Science University, said: “I am encouraged by the signals of efficacy observed from the Phase 3 post-hoc analyses of vilobelimab in pyoderma gangrenosum. The role of targeting C5a/C5aR aligns with prior mechanistic work supporting its use for this devastating inflammatory dermatological disease, which has no FDA-approved therapy. Given the significant unmet need and lack of approved therapies, I am hopeful these findings will motivate further investigation of this targeted approach.”
Benjamin Kaffenberger, MD, Associate Professor, Dermatology, The Ohio State University Wexner Medical Center, said: “Pyoderma gangrenosum remains a difficult-to-treat rare disease with high unmet medical need. The data for vilobelimab suggest an overall treatment effect, even if the primary endpoint may not have been achieved within the six-month timeframe required in this first-of-its-kind Phase 3 trial. Unfortunately, there is not a successful precedent for conducting a pivotal Phase 3 placebo-controlled study in PG, and I believe the futility leading to early discontinuation relates to challenges in trial design rather than lack of efficacy of the therapy. I believe that blocking C5a/C5aR in this neutrophilic disease continues to make scientific and clinical sense and that there is a strong justification to move forward.”
As next steps, InflaRx anticipates meeting with the FDA to discuss a potential path forward for vilobelimab in PG, including the use of alternative endpoints that could be utilized for potential future clinical studies. At this time, in an effort to prioritize izicopan (INF904) development, InflaRx does not expect to deploy significant resources towards future vilobelimab development in PG on its own and will instead consider doing so in collaboration with a partner.
Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism of the innate immune system, which is not the case for molecules blocking C5. In pre-clinical studies, vilobelimab has been shown to control the inflammatory response-driven tissue and organ damage by specifically blocking C5a as a key “amplifier” of this response.
InflaRx (Nasdaq: IFRX) is a biopharmaceutical company pioneering anti-inflammatory therapeutics by applying its proprietary anti-C5a and anti-C5aR technologies to discover, develop and commercialize highly potent and specific inhibitors of the complement activation factor C5a and its receptor, C5aR. C5a is a powerful inflammatory mediator involved in the progression of a wide variety of inflammatory diseases. InflaRx has developed vilobelimab, a novel, intravenously delivered, first-in-class, anti-C5a monoclonal antibody that selectively binds to free C5a and has demonstrated disease-modifying clinical activity and tolerability in multiple clinical studies. InflaRx is also developing izicopan (INF904), an orally administered small molecule inhibitor of C5a-induced signaling via the C5a receptor.
InflaRx was founded in 2007, and the group has offices and subsidiaries in Jena and Munich, Germany, as well as Ann Arbor, MI, USA. For further information, please visit www.inflarx.de. InflaRx GmbH (Germany) and InflaRx Pharmaceuticals Inc. (USA) are wholly owned subsidiaries of InflaRx N.V. (together, InflaRx).
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