Pegcetacoplan

--- 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. CLEVELAND, May 19, 2025 (GLOBE NEWSWIRE) -- 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." Figure. NovelMed Scientist Prepares Complement Test Assays to Support Clinical Development of Ruxoprubart (NM8074) for Paroxysmal Nocturnal Hemoglobinuria (PNH). 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.” Clinical Study Overview and Efficacy Summary in PNH 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.” Paroxysmal Nocturnal Hemoglobinuria (PNH) 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 (NM8074) 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 Therapeutics ( www.novelmed.com ) 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). We are committed to delivering life-changing therapies to patients across hematology, ophthalmology, nephrology, dermatology, and neurology. NovelMed is currently seeking partnerships to advance the development of Ruxoprubart to approval in several chronic diseases. We are open to discussions regarding investment, out-licensing, or acquisition. For more details regarding our progress, please visit www.novelmed.com/news . Watch our introductory Video to learn more about NovelMed. Contact: Ya Gao, MS NovelMed Communication Team BD@novelmed.com (216) 440 2696 Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis https://www.globenewswire.com/NewsRoom/AttachmentNg/ae2c0bfc-ff88-486d-a796-f2977947c8a4 Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis (Available at https://www.globenewswire.com/NewsRoom/AttachmentNg/ae2c0bfc-ff88-486d-a796-f2977947c8a4) Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

关注并星标CPHI制药在线       在创新药市场中，补体药物是一个重要领域，也是研发壁垒较高的一个赛道。但鉴于其拥有巨大的应用前景，近年来补体药物的研发进入快车道，其适应症范围也在逐步拓展。近日，诺华的补体因子B（CFB）抑制剂伊普可泮（Iptacopan，Fabhalta）获NMPA批准，用于成人C3肾小球病（C3G）的治疗，这是补体药物在肾病治疗领域解锁的又一块拼图。该适应症的获批，彰显了补体药物的巨大潜力，同时也将其研发热度再次掀起。01伊普可泮的适应症版图伊普可泮是一款同类首创的CFB抑制剂，通过与补体旁路途径中的FB结合，调节C3的裂解、下游效应物的产生和末端途径的放大，控制C3b介导的血管外溶血和末端补体介导的血管内溶血。2023年12月，伊普可泮首次获FDA批准，治疗成人阵发性睡眠性血红蛋白尿症（PNH）。PNH是一种罕见的血液系统疾病，发病率约为每百万人口1～10例，已被纳入我国《第一批罕见病目录》。该病临床主要表现为血管内溶血、骨髓衰竭和高风险并发血栓等，虽为良性血管内溶血性疾病，但严重者可危及生命。在补体抑制剂获批前，PNH主要以支持治疗为主，包括红细胞输注、补充造血原料、糖皮质激素和雄激素的使用以及免疫抑制剂的应用。但是传统支持治疗疗效有限，多数患者无法摆脱输血依赖，且患者10年总生存率仅70.7%~77.6%，生存率及生活质量亟待提高。伊普可泮的上市，改变了PNH的治疗局面。在APPOINT-PNH研究中，在未接受过补体抑制剂治疗的成人PNH患者中，给予伊普可泮单药治疗后，92%的患者在未输注红细胞的情况下血红蛋白水平相较基线增加≥2g/dL，近2/3患者的血红蛋白恢复至正常水平（≥12g/dL），98%的患者避免输血。同时，患者的疲劳症状表现出具有临床意义的改善。而且伊普可泮避免患者不断往返于居住地和医院，提高了患者依从性，使PNH从一个几乎不可治愈、危及生命的严重疾病转变为可接受长期管理的慢性疾病。2024年8月，FDA再次批准伊普可泮新适应症，用于降低成人IgA肾病（IgAN）患者的蛋白尿水平，这些患者有疾病迅速进展的风险。IgAN是一种罕见的异质性、进行性肾脏疾病。全世界每年每百万人中约有25人被新诊断为IgAN，由于患者具有持续较高水平的蛋白尿，因此可能在10年内进展为肾衰竭。在III期APPLAUSE-IgAN研究中，与安慰剂组相比，伊普可泮组患者的蛋白尿水平减少了38.3%（p<0.0001），并减缓了肾功能下降速度。而且伊普可泮的安全性和耐受性良好，与既往研究一致。伊普可泮的这一突破性进展，为IgA肾病的精准治疗开辟了新途径。2025年3月，伊普可泮获FDA批准，用于治疗成人C3肾小球病（C3G），以减少蛋白尿。这是第一个获批上市的C3G疗法。C3G是一种极其罕见的进行性肾脏疾病，多见于儿童和年轻人。每年全球每百万人中约有1-2人确诊。大约一半的C3G患者在诊断后10年内进展为肾衰竭，需要终身透析和/或肾移植。在III期APPEAR-C3研究中，评估了伊普可泮（200mg，每日2次）在原发性C3G患者中的疗效和安全性。结果显示，伊普可泮可迅速降低蛋白尿，最早在第14天见效，并持续至第12个月。同时，伊普可泮在研究中也表现出了良好的耐受性和安全性。伊普可泮自上市以来，短短两年多时间，已顺利获批三项适应症，曾被行业媒体Evaluate列为10款值得关注的潜在重磅疗法之一。02打破治疗困局，补体药物围攻罕见病补体系统是人体先天免疫系统的一部分，由大约50种蛋白质及蛋白质片段组成，主要由肝脏细胞和巨噬细胞产生，具有增强抗体、吞噬细胞、清除生物体中的微生物和受损细胞、攻击入侵病原体等能力。正常情况下，补体处于无活性状态，只有被某些因子激活后才产生具有生物活性的裂解片段，作用于相应靶细胞的受体而发挥生物学效应。补体被活化后产生大量具有活性的裂解产物如：C1q、C3a、C3b、C5a、C5b-9等。这些裂解产物有介导细胞溶解、调节细胞吞噬、清除免疫复合物和损伤凋亡细胞等生物学效应。补体激活途径主要有三条：经典激活（Classical pathway），凝集素激活（Lectin pathway）和旁路激活（Alternative pathway）。经典激活是由抗原抗体复合物结合C1q启动；凝集素激活发生在感染早期，机体炎症反应诱导肝细胞释放急性期蛋白MBL，C反应蛋白等。旁路激活是指病原微生物直接从C3激活。由于补体网络极其复杂，他在激活与调控之间维持着精妙的平衡，因此补体的选择性抑制十分重要，相关药物研发因此困难重重。目前已获批上市的补体药物有10款，适应症多集中于PNH等罕见病。2007年，由Alexion（于2020年被阿斯利康收购）研发的Soliris（eculizumab）获批上市，是全球获批的首 款C5补体抑制剂，也成为了当时PNH首个也是唯一的治疗药物。Soliris成为了全球最畅销的罕见病药物之一。目前，除PNH外，Soliris已批准多种罕见病，包括：非典型溶血尿毒症综合征（aHUS）、全身型重症肌无力（gMG）、视神经脊髓炎谱系障碍（NMOSD）。2018年，阿斯利康的第二代、长效C5补体抑制剂Ultomiris（ravulizumab）获FDA批准上市。与Soliris相比，Ultomiris每年需要的输液次数减少，并具有良好的疗效和安全性。目前该药已批准的适应症包括PNH和aHUS。Ultomiris的业绩依然不容小觑，2020年销售额就达到了10.77亿美元。在阿斯利康两款重磅药物影响下，投入补体药物研发的药企越来越多。从2021年开始，补体药物研发进入快车道。2021年5月，Apellis Pharmaceuticals的C3补体抑制剂Empaveli（pegcetacoplan）获FDA批准上市，用于治疗PNH成人患者，成为首个FDA批准的用于治疗PNH的C3靶向疗法。2021年9月，安进和CSL Vifor共同开发的阿伐可泮（avacopan）获FDA批准上市，用于联合包括糖皮质激素在内的标准治疗方案治疗成人活动性严重ANCA相关血管炎（MPA和GPA）。阿伐可泮是一种补体5a受体（C5aR）拮抗剂，可抑制C5aR和过敏毒素C5a之间的相互作用，阻断C5a介导的中性粒细胞激活和迁移。阿伐可泮是FDA批准的首款口服补体5a受体拮抗剂。2022年，赛诺菲的补体C1s单抗Enjaymo(Sutimlimab)获FDA批准上市，用于冷凝集素病（CAD)患者降低由于溶血导致的红细胞输注需求。Sutimlimab通过阻断经典补体途径中C1s蛋白的功能而发挥抑制溶血的作用，是FDA批准的首 款用于治疗CAD的补体C1s抗体。此后几年，安斯泰来的Izervay（avacincaptad pegol）、再生元的Veopoz（Pozelimab）、UCB的Zilbrysq相继获批上市，其中Izervay是一款旨在抑制补体C5蛋白的聚乙二醇化RNA适配体；Veopoz则是一款新一代补体C5单抗；Zilbrysq是一款新型大环肽类C5补体抑制剂。总之，目前已上市的补体药物大多采用从罕见血液疾病切入的研发策略，逐步向常见病领域跃迁。03从罕见病到常见病，补体药物厚积薄发由于补体系统在免疫调节、炎症反应等过程中都起着重要作用，近年来，补体药物不断向常见病领域探索。2023年，Apellis Pharmaceuticals的pegcetacoplan获FDA批准，成为第一款治疗地图样萎缩（GA）的药物。GA是干性年龄相关性黄斑变性（AMD）的一种晚期形式。AMD是一种影响眼后部部分黄斑的疾病，一些AMD患者最终会发展为GA。GA可导致进行性和永久性视力丧失。而且如果患者一只眼睛患有GA，则很有可能在另一只眼睛中也患上该疾病，严重影响患者生活质量。据悉，美国近2000万成年人患有某种形式的年龄相关性AMD，其中有100万人患有GA。全球GA患者人数估计超过500万。Pegcetacoplan在GA上的突破，标志着补体药物在常见病领域的破冰。2025年2月，安斯泰来宣布FDA批准其Izervay用于治疗GA的补充新药申请（sNDA）。经此次批准，Izervay的给药持续时间再无限制——为医生和患者管理GA提供了更大的灵活性。这些成果验证了补体系统在视网膜疾病治疗中的作用，全方位展示补体药物的广泛治疗益处。在经过数十年的探索后，补体药物的开发终于迎来了快速爆发期，靶点从C5拓展到C3、C5a、C1s、CFB等，药物类型也从单克隆抗体拓展到环肽、小分子、核酸药物等，适应症更是从罕见病向常见病拓展。总的来说，补体药物的研发虽然困难，但非常值得持续探索。主要参考资料：     1.https://www.novartis.com/sites/novartis_com/files/q2-2024-investor-presentation.pdf.2.Risitano AM, Röth A, Soret J, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021;8(5):e344-e354.3.Peffault de Latour R, Röth A, Kulasekararaj AG, et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2024 Mar 14;390(11):994-1008.       作者简介:@小饼，药学硕士，现为疾控工作人员，每天游走于纷繁复杂的数据里，深感自己渺小的同时，又庆幸能够见证中国生物医药发展的黄金时代。希望和各位共同学习、提高。END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~