Danicopan

--- Ruxoprubart (NM8074) met all clinical endpoints, offering a safe, differentiated treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH). Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare hematological (Blood) disorder. Regulatory approval for the Phase II trial in PNH subjects was granted based on the safety profile of healthy subjects in the Phase I trial. Interim results from this 12-subject, three-month, multi-dose Phase II efficacy trial are compelling. The drug was safe and well-tolerated in all treated PNH subjects with expected safety & efficacy, meeting all clinical endpoints with no reported side effects. In this efficacy trial, Ruxoprubart: Protected PNH Red Blood cells against lysis and enabled complete transfusion avoidance, meeting the primary endpoint. Increased hemoglobin levels above baseline by 1.4 to 2.0 g/dL in most subjects, with some showing intra-subject hemoglobin increase of 1.5 to 4.3 g/dL, exceeding the threshold set for the primary endpoint. An average hemoglobin increase of >1.6 g/dL was observed across the cohort from baseline to the end of the treatment period. Reduced LDH levels to baseline, meeting the primary efficacy endpoint. Significantly increased PNH Type III clone size by protecting PNH Red Blood Cells from complement-mediated lysis. Allowed normal pathogenic clearance in all treated PNH subjects, as infection cleared as expected. The regulatory agency has recently approved a once-weekly subcutaneous protocol for Ruxoprubart — allowing for self-administration and offering a distinct advantage over Apellis, which requires twice-weekly dosing. Ruxoprubart effectively inhibited the Alternative Pathway (AP) without affecting the Classical Pathway (CP) in the trial. More importantly, the FDA has granted Orphan Drug Designation (ODD) to Ruxoprubart for treating PNH. A Breakthrough Therapy Designation (BTD) application for Ruxoprubart in PNH will soon be filed for FDA review. Ruxoprubart is set to be developed as a novel treatment for several complement-mediated disorders, including but not limited to renal, hematological, dermatological, and ocular diseases. May 19, 2025 -- NovelMed is pleased to announce positive 12-week interim results from the ongoing multi-dose Phase II trial of Ruxoprubart, a novel complement-targeting immunotherapy, in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). These interim data demonstrate that Ruxoprubart, administered as monotherapy, was safe, well-tolerated, and met all primary efficacy endpoints. Ruxoprubart achieved transfusion avoidance, increased hemoglobin levels, reduced LDH, and increased PNH clone size — key outcomes that contributed to improved disease control and enhanced quality of life for PNH patients. “The promising interim results from our Phase II PNH study solidify Ruxoprubart as a novel treatment for patients with advanced hematological conditions, offering hope where existing therapies fall short. This achievement not only underscores our commitment to advancing Ruxoprubart, an immunotherapy for PNH, but also marks a significant step toward addressing critical unmet needs within this patient population," said Dr. Rekha Bansal, CEO. "I extend my sincere gratitude to the PNH subjects and investigators whose dedication has been instrumental in this success. We are eager to present our findings to regulatory authorities and proceed with the Phase III trial." Ruxoprubart works by binding to Bb and selectively inhibiting the protease activity of the Alternative Pathway C3 convertase, while preserving the Classical Pathway. By acting proximally in the Alternative Pathway, Ruxoprubart provides complete control over both intravascular and extravascular hemolysis, resulting in marked increases in hemoglobin levels observed in this trial. These findings support the drug’s advancement as a novel, next-generation immunotherapy for the treatment of PNH and a broad range of hematological, renal, inflammatory, and ocular diseases. “We are excited to announce that our Alternative Pathway strategy for treating PNH is delivering exceptional results,” said Mr. Alex Kumar, Chief Strategy Advisor at NovelMed. “These data reinforce our confidence as we look forward to working with the regulatory agency to bring Ruxoprubart to PNH patients without delay. Our mission is to transform the lives of chronically ill patients for whom an ideal treatment has yet to be discovered.” This Phase II trial was initiated following the successful completion of a Phase I study involving 40 (forty) healthy volunteers. Ruxoprubart was well tolerated across all dose levels, ranging from 0.3 to 20 mg/kg, with no safety concerns. The drug demonstrated selective inhibition of the Alternative Pathway through Bb binding, without affecting the Classical Pathway. These promising safety findings paved the way for regulatory approval to initiate a Phase II study in patients with PNH. This ongoing 12-week clinical trial of Ruxoprubart is an open-label, multi-dose study in treatment-naïve adult subjects with PNH. The primary objectives are to evaluate the safety, tolerability, and efficacy of Ruxoprubart as a monotherapy in the Alternative Pathway-mediated lysis of Red Blood Cells. To date, 10 out of 12 PNH subjects have completed the study. Subjects 11 & 12 have been enrolled to complete the two-cohort trial. Interim results confirm that Ruxoprubart achieved all primary efficacy endpoints, delivering sustained clinical benefit in PNH. The primary efficacy endpoints include: Transfusion Avoidance: PNH patients typically require multiple blood transfusions to maintain normal hemoglobin levels. Ruxoprubart effectively protected PNH Type III cells from Alternative Pathway-mediated destruction, resulting in complete transfusion avoidance and successfully meeting the primary efficacy endpoint. Hemoglobin Increase: PNH patients experience reduced hemoglobin levels, leading to severe anemia. Ruxoprubart increased hemoglobin levels above baseline by 1.4 to 2.0 g/dL in most subjects, with some showing intra-subject increases ranging from 1.5 to 4.3 g/dL, surpassing the efficacy threshold defined for the primary endpoint. An average increase of >1.6 g/dL in hemoglobin was observed across the cohort from the beginning to the end of the treatment period. LDH Reduction: PNH patients experience severe lysis of Red Blood Cells (RBCs), leading to elevated lactate dehydrogenase (LDH) levels. By controlling complement-mediated hemolysis, Ruxoprubart reduced LDH levels to baseline, achieving the primary efficacy endpoint. Preservation of PNH Cells: Continuous lysis of Red Blood Cells in PNH leads to a dramatic reduction in total RBC count, often exceeding 80 to 90%. By effectively preventing this lysis, Ruxoprubart significantly preserved PNH cells, resulting in a substantial increase in the total PNH clone size and hemoglobin, successfully meeting the primary efficacy endpoint. Pathogenic Clearance: As expected, Ruxoprubart facilitated effective pathogenic clearance across all treated PNH subjects. In summary, the observed changes in efficacy parameters support the drug's mechanism of action and validate Ruxoprubart’s potential as a highly effective monotherapy for PNH. “We are thrilled to share these data, which demonstrate the potential of Ruxoprubart in advanced PNH, and look forward to working with regulatory authorities to bring this new immunotherapy to this patient community,” said Mr. Robert Bard, Vice President of Regulatory Affairs at NovelMed. “It’s very clear that we are on a promising path with exciting Phase II data in this serious hematological disorder.” PNH is a rare, acquired hematologic disorder in which Red Blood Cells lack protective surface proteins due to a mutation in the phosphatidylinositol glycan class A (PIGA) gene, leaving them vulnerable to complement-mediated destruction. In healthy individuals, Type I RBCs express complement regulatory proteins and are fully protected from complement-mediated destruction. In contrast, PNH patients have a significant percentage of Type III RBCs, which completely lack these protective proteins and are therefore highly susceptible to Alternative Pathway-mediated lysis. PNH is primarily an Alternative Pathway-mediated disease, with no involvement of the Classical or Lectin pathways in its pathology. Key laboratory markers indicative of disease progression include reduced Type III Red Blood Cells, low hemoglobin, elevated lactate dehydrogenase (LDH), and an increased need for blood transfusions. These markers reflect the underlying hemolytic anemia, which in turn leads to debilitating symptoms such as chronic fatigue, pain, jaundice, and organ damage. As the disease progresses, it significantly affects the patient’s quality of life and can ultimately result in life-threatening complications and death if not properly managed. While Soliris® (eculizumab) is the current FDA-approved standard of care for PNH – administered via intravenous infusion to provide C5 blockade – clinical limitations persist. Up to 88% of Soliris-treated patients continue to experience persistent anemia, with more than one-third of them requiring blood transfusions at least once every year. Despite its effectiveness in some patients, Soliris does not fully address the needs of many patients, as a significant proportion remain anemic, fatigued, and require blood transfusions, highlighting the need for specific, effective, and comprehensive therapies. Nearly all FDA-approved therapies for PNH and other complement-mediated disorders, oral or intravenous, suffer from the well-documented Black Box warning label because of the broad immunosuppression of the Classical Pathway, elevating the risk of life-threatening infections. Ruxoprubart offers a selective, upstream, and targeted approach to Alternative Pathway inhibition, without compromising the Classical Pathway, offering the best-in-class novel therapy. These attributes position Ruxoprubart as a safer and more effective treatment for patients with PNH. Ruxoprubart, an engineered human immunoglobulin, exhibits dual specificity: 1) it blocks only the Alternative Pathway, dysregulated by the disease, and 2) it binds Bb which has no binding to Factor B. Ruxoprubart met all primary endpoints in the interim evaluation of the ongoing Phase II clinical trial in PNH, positioning it as the first immunotherapy in this indication with the potential for approval without a Black Box warning. This immunotherapy has demonstrated a safe and well-tolerated profile across all five cohorts in the Phase I trial, including the highest dose of 20 mg/kg. Our findings confirm that the drug selectively blocks the Alternative Pathway. This differentiated, novel mechanism sets Ruxoprubart apart from other complement blockers (Soliris®, Ultomiris®, Empaveli®, Voydeya®, and Fabhalta®) currently approved or in development worldwide. Voydeya®, which received FDA approval in 2024 as a combination therapy, was developed by Achillion and acquired by AstraZeneca for $930 million. Despite its limited clinical efficacy, Voydeya®'s reliance on co-administration with a C5 inhibitor restricts its potential as a standalone therapy. Unlike Fabhalta®, which targets Factor B, Ruxoprubart (NM8074) binds to Bb, which is generated only upon activation of the Alternative Pathway, offering a unique mechanism of action as monotherapy. As a novel monotherapy with a unique, upstream, and pathway-specific mechanism, Ruxoprubart is emerging as a best-in-class candidate for the treatment of PNH and numerous complement-mediated diseases. NovelMed is a clinical-stage biopharmaceutical company dedicated to developing innovative novel biologics (immunotherapies) to treat a wide range of complement-mediated diseases. NovelMed proudly leads the development of Alternative Pathway-specific antibodies (NM8074, NM5072, and NM8070) to address a wide range of chronic complement-mediated disorders. The company is actively conducting a Phase II clinical trial in treatment-naïve PNH subjects to expedite the availability of this promising treatment. Additionally, the FDA has approved Phase II studies for several rare diseases, including but not limited to Atypical Hemolytic Uremic Syndrome (aHUS), C3 Glomerulopathy (C3G), IgA Nephropathy (IgAN), ANCA-Associated Vasculitis (AAV), and Dermatomyositis (DM). The content above comes from the network. if any infringement, please contact us to modify.

日前，英国医药咨询公司IDEA Pharma更新了2025年全球制药创新指数榜单和全球制药发明指数榜单。在这份被誉为“医药界创新风向标”的榜单中，礼来夺回创新指数冠军，阿斯利康则再次问鼎发明指数榜首，坐实“医药发明之王”称号，比利时制药公司UCB凭借其在免疫学与罕见病领域的突破性进展，成功跻身创新指数十强。而糖尿病巨头诺和诺德遭遇滑铁卢，创新指数排名暴跌至第九位，发明指数更是无缘前十。其市值从6400亿美元高点腰斩至约3000亿美元，而其任职八年的CEO也将离职，折射出GLP-1赛道激战下的行业变局。图片来源：参考资料1创新指数（Pharmaceutical Innovation Index），代表了药企的产品价值，指标为过去3-5年上市新品的数量和销售额占比；过去五年营收增速和研发投入占比；以及与公司的组织架构调整、收并购事件和投融资事件。发明指数（Pharmaceutical Invention Index），代表了药企的研发水平，着眼于制药企业研发管线的广度和深度，以及研发管线中在研疗法的新颖性。表1 创新指数TOP10数据来源：参考资料1表2 发明指数TOP10数据来源：参考资料1礼来问鼎创新指数榜首礼来此次登顶得益于多领域突破：肥胖症药物Zepbound（替尔泊肽）拓展新适应症，成为首个获批治疗中重度阻塞性睡眠呼吸暂停的创新疗法；阿尔茨海默病新药Kisunla为早期认知障碍患者带来曙光；特应性皮炎药物Ebglyss获批上市；32亿美元收购Morphic Therapeutic强化免疫管线；LillyDirect平台降本增效等战略举措，构建起从研发到交付的创新生态闭环。其排名从去年第四跃居榜首。UCB凭借“免疫-神经-罕见病”三线突破首入十强：双靶点IL-17A/F抑制剂Bimzelx（比美吉珠单抗）在银屑病关节炎、化脓性汗腺炎等慢性炎症疾病中展现四年长效获益；重症肌无力双星Zilbrysq与Rystiggo实现症状持续控制；抗CD40L药物Dapirolizumab pegol在系统性红斑狼疮Ⅲ期临床告捷，奠定其在罕见自身免疫疾病领域的领先地位。此外，默沙东凭借对Keytruda的持续探索，从第十飙至亚军。阿斯利康与罗氏并排第三；辉瑞守住前五。排名前十的还有：再生元、强生、诺和诺德、诺华、福泰制药。阿斯利康拿下发明指数冠军阿斯利康取代了强生公司位列发明指数榜首。肿瘤领域仍是阿斯利康的最重要的创新引擎：PD-L1抑制剂英飞凡（度伐利尤单抗）多癌种拓展、第三代EGFR-TKI泰瑞沙（奥希替尼）使Ⅲ期肺癌患者死亡风险降低84%、与第一三共合作的ADC药物Enhertu（德曲妥珠单抗）在HER2低表达乳腺癌治疗中展现显著生存获益。此外，阿斯利康在心血管、罕见病等领域也有突破，包括Fasenra（贝那利珠单抗）与Voydeya的新适应症获批，更彰显其全领域创新实力。强生今年跌至第二名，莫德纳（Moderna）位居第三，罗氏和再生元排名显著跃升，分别从去年的第17名和第8名上升至并列第4名。从十几名跃升至前十名的还有排名第8的葛兰素史克（GSK），以及排名第10的百济神州（BeOne Medicines）和勃林格殷格翰（Boehringer Ingelheim）。其他进入发明指数前十名的还有排名第6的礼来公司、第7名的默沙东和第9名的辉瑞。IDEA Pharma首席执行官Mike Rea指出：“伟大企业的卓越在于持续性而非偶然性。”榜单数据印证：创新指数前十中六家为2024年原班人马，发明指数前十仅更替三席，头部药企已构建系统化创新体系。随着医药创新进入深水区，谁能以更卓越的研发与商业化能力创造医疗价值？答案或许就藏在这份榜单变迁中：那些将科学洞察转化为临床价值、以患者需求驱动创新的企业，将在行业变革中立于不败之地。参考来源：1.https://www.ideapharma.com/insights/launching-the-14th-annual-pharmaceutical-innovation-index2.https://www.fiercepharma.com/pharma/eli-lilly-out-performs-novo-market-it-also-replaces-its-rival-idea-innovation-rankings声明：本内容仅用作医药行业信息传播，不代表药智网立场。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石合作、投稿 | 马老师 18323856316（同微信） 阅读原文，是受欢迎的文章哦