Vilobelimab

摘要：曾因三期临床试验无效而终止的 InflaRx 公司 C5a 抗体药物维洛贝利单抗（vilobelimab），在对废弃试验数据的深度分析后迎来转机。这款已获新冠重症紧急使用授权的药物，在罕见皮肤病坏疽性脓皮病（PG）治疗中显现积极疗效信号。InflaRx 计划与 FDA 沟通新的研发路径，并寻求合作伙伴共同推进该适应症的后续开发。试验终止后的意外发现 2025 年 5 月，InflaRx 因独立数据监测委员会判定试验无效，终止了维洛贝利单抗治疗溃疡性坏疽性脓皮病的三期临床试验，当时仅分析了首批 30 名患者数据。 然而，年底公布的事后分析带来惊喜。对试验终止时入组的 54 名患者（其中 30 人完成半年治疗）的全面评估显示，该药物在多个关键指标上呈现积极趋势。主要终点方面，维洛贝利单抗组连续两次随访中目标溃疡完全愈合率为 20.8%，高于安慰剂组的 16.7%；次要终点表现更突出，30% 的用药患者实现所有溃疡完全愈合的疾病完全缓解，而安慰剂组仅为 5.6%，同时 36.4% 的用药患者在 26 周时溃疡体积缩小 50% 以上，安慰剂组这一比例为 16.7%。 进一步的统计分析显示，从治疗 14 周到 26 周，维洛贝利单抗与安慰剂相比存在显著治疗差异，且超过 26 周的给药可能带来更好疗效。俄亥俄州立大学韦克斯纳医学中心的本杰明・卡芬伯格博士指出，PG 领域尚无成功的三期安慰剂对照试验先例，此前试验终止源于设计挑战而非药物无效。药物特性与研发规划 维洛贝利单抗的独特机制为其提供了理论支撑。该药物能精准阻断免疫系统补体级联反应中的 C5a 片段，且不影响膜攻击复合物的形成 —— 这一先天免疫系统的重要防御机制得以保留。目前，该药物已以 Gohibic 为商品名，获美国 FDA 紧急使用授权用于治疗特定新冠重症患者，去年的 PG 试验终止并未影响其新冠治疗适应症状态。 InflaRx 首席执行官尼尔・里德曼博士表示，数据分析证实了 C5a/C5aR 通路在 PG 等中性粒细胞性皮肤病中的作用。公司计划近期与 FDA 会面，探讨以替代终点推进研发的可能性。但鉴于资源将优先投入口服小分子候选药物 izicopan 的开发，InflaRx 明确表示不会单独为维洛贝利单抗的 PG 适应症投入大量资源，后续研发将通过合作模式开展。管线布局与资金状况 izicopan 作为另一款补体系统抑制剂，目前在慢性自发性荨麻疹（CSU）和化脓性汗腺炎（HS）适应症上已取得二期 a 期积极数据，InflaRx 将其定位为 “具有变革性的同类最佳免疫调节药物”，并预测这两个适应症各自市场规模有望超 10 亿美元。 财务方面，截至 2025 年夏季，InflaRx 拥有约 5370 万欧元现金及等价物，外加 4070 万欧元有价证券，资金可支撑运营至 2027 年。在聚焦核心管线的同时，维洛贝利单抗在 PG 适应症上的潜力，或将通过合作模式续写新的研发篇章。 参考来源：https://www.fiercepharma.com/pharma/after-scrapped-trial-inflarx-could-tap-partner-revive-development-covid-drug-rare-skin 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

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). The content above comes from the network. if any infringement, please contact us to modify.