Ravulizumab-CWVZ

--- Precision Bb Targeting, Robust Efficacy, Transfusion Independence, Excellent Safety in Phase II PNH Study, and Subcutaneous Administration Key Highlights: Monotherapy and Clinical Outcomes The 12-16-week open-label study evaluated Ruxoprubart as monotherapy in treatment-naïve PNH patients. Key findings include: Hemoglobin (Hb) Improvement: Hemoglobin levels increased by 1.5–2.7 g/dL, with an average rise of ~2.13 g/dL during weekly dosing, reflecting meaningful correction from the severely depressed baseline common in untreated PNH. Complete Transfusion Independence: Throughout the weekly dosing period, 100% of patients required no blood transfusions, demonstrating effective control of hemolysis and clinically meaningful correction of anemia. PNH Red Blood Cells (RBCs) Survival & Expansion: PNH RBC populations expanded to up to 94% of their maximum level. This is consistent with near-complete suppression of ongoing complement-mediated hemolysis, a core driver of anemia and fatigue. Biochemical Control (LDH): Lactate Dehydrogenase (LDH) levels were significantly reduced, reflecting biochemical control of intravascular hemolysis (IVH). Quality-of-Life (QoL) Gains: Patient‑reported outcomes, including the Functional Assessment of Chronic Illness Therapy (FACIT) and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, showed meaningful improvements across fatigue, pain, and overall functional capacity. Safety and Tolerability: The therapy was well-tolerated with no drug-related Adverse Events (AEs) or Serious Adverse Events (SAEs) observed. Orphan Drug Designation: Ruxoprubart holds U.S. FDA Orphan Drug Designation (ODD) for PNH, highlighting its potential to address this rare and life-threatening condition. CLEVELAND, March 09, 2026 (GLOBE NEWSWIRE) -- NovelMed Therapeutics Inc., a clinical-stage biopharmaceutical company specializing in alternative pathway (AP) complement-mediated therapies, today announced two major milestones in the clinical development of Ruxoprubart (NM8074) for Paroxysmal Nocturnal Hemoglobinuria (PNH). The company has received regulatory clearance to initiate a Phase II study for the subcutaneous (SC) route of administration, designed as a convenient, weekly, self-administered injection. Concurrently, NovelMed reported the full results of its Phase II intravenous (IV) monotherapy study in treatment-naïve adult patients with PNH. The study met all efficacy endpoints, including significant hemoglobin improvement and complete transfusion avoidance, with an exceptional safety profile. “These milestones validate both our clinical progress and our development strategy,” said Dr. Rekha Bansal, Chief Executive Officer of NovelMed. “Regulatory clearance of the SC route represents the next logical step toward a patient-friendly treatment option, while our monotherapy data demonstrate the strong, consistent efficacy and tolerability of targeting Bb. We are now progressing into the next phase of clinical development.” Advancing Two Complementary Tracks in PNH NovelMed is progressing Ruxoprubart through two distinct delivery methods to maximize patient access and convenience: Subcutaneous (SC) Administration: Cleared for Phase II Development The regulatory agency has cleared the SC route of administration, enabling a planned, weekly self-injection regimen at home. SC trials are planned but have not yet been initiated. This approach is expected to reduce patient and caregiver burden by eliminating the need for IV infusions in a clinical setting. Intravenous (IV) Monotherapy: Treatment-Naïve PNH Patients The successful completion of the intravenous Phase II study establishes Ruxoprubart as a potent monotherapy capable of addressing the core drivers of PNH without adjunctive treatment. “Ruxoprubart has proven its potential as a definitive monotherapy, delivering exceptional efficacy without compromise,” said Mr. Alex Kumar, Chief Strategy Advisor. “Coupled with FDA Orphan Drug Designation status and regulatory clearance for SC dosing, we have a clear, accelerated path forward. NovelMed is now uniquely positioned to lead the next generation of precision complement therapeutics on a global scale.” Precision Targeting: The Bb Mechanism and Differentiation PNH is an AP-driven hemolytic disorder. Ruxoprubart (NM8074) is a first-in-class monoclonal antibody engineered for precision targeting of Bb, the proteolytically activated catalytic fragment generated upon AP activation. By binding Bb rather than native Factor B, Ruxoprubart delivers precise AP-selective inhibition while preserving the Classical Pathway (CP), which remains essential for protecting patients from infections. “The Phase II intravenous results demonstrate a clinical efficacy and safety pro aligns well with FDA expectations for monotherapy development in PNH,” said Mr. Robert Bard. “With the SC route now cleared for evaluation under our Phase II program, we are advancing along a well-defined regulatory path. This progress brings us closer to enabling patient-friendly, self-administered treatment options supported by a mechanism designed for pathway-selective precision.” Competitive Landscape at a Glance Ruxoprubart (NovelMed): Targets activated Bb (FDA Orphan Drug Designation Holder). A precision monotherapy that provides selective AP inhibition while preserving the CP for host defense. Soliris® / Ultomiris® (AstraZeneca): Targets C5. A distal blocker of both AP and CP that fails to prevent C3b deposition, which leads to persistent anemia. Empaveli® / Syfovre® (Apellis): Targets C3. A proximal blocker that provides broad inhibition of both AP and CP, addressing C3b-mediated EVH but impacting overall complement surveillance. Fabhalta® (Novartis): Targets native Factor B. A proximal blocker that lacks precision by targeting the native protein rather than the proteolytically activated Bb fragment. Voydeya® (AstraZeneca): Targets Factor D. A proximal blocker, strictly approved as an add-on therapy to C5 inhibitors rather than a standalone monotherapy. Key Pillars of the Regulatory Strategy Monotherapy Treatment: Ruxoprubart has demonstrated the ability to meet all primary endpoints as a standalone treatment. This allows for a more direct regulatory path, as the drug does not need to be tested or approved alongside existing C5 inhibitors to prove its value. Subcutaneous (SC) Administration: The regulatory clearance for the SC route is a major milestone. Having passed rigorous safety and manufacturing reviews, Ruxoprubart is now cleared for human trials using at-home injections. This shifts the treatment model from clinical IV infusions to a more convenient, patient-controlled approach. Precision Targeting of the Bb: Ruxoprubart selectively targets the AP while keeping the CP intact. This "selective precision" is designed to maintain the body’s natural ability to fight infections, a differentiated safety pro supports the case for expedited regulatory designations like Fast Track or Breakthrough Therapy. Figure. Complement-mediated destruction of red blood cells in paroxysmal nocturnal hemoglobinuria (PNH). About Paroxysmal Nocturnal Hemoglobinuria (PNH) Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired, and life-threatening hematologic disorder caused by a somatic mutation in the PIGA gene. This mutation results in the deficiency of GPI-anchored complement regulatory proteins, specifically CD55 and CD59, which act as protective shields for RBCs. Without these proteins, RBCs are highly vulnerable to persistent attack by the AP of the complement system, leading to chronic intravascular and extravascular hemolysis. This ongoing destruction manifests clinically as severe anemia, dangerously elevated Lactate Dehydrogenase (LDH) levels, and a significantly increased risk of life-threatening thrombosis and renal impairment. Effective treatment is measured by stabilization of hemoglobin and the expansion of the PNH RBC clone, indicating that these cells are successfully protected from complement-mediated attack. About NovelMed Therapeutics NovelMed Therapeutics Inc. is a clinical-stage biopharmaceutical company dedicated to developing next-generation immunotherapies that selectively target the complement AP. The company has pioneered a site-specific approach by engineering monoclonal antibodies, such as its lead candidates Ruxoprubart (NM8074) and NM5072, to target proteolytically activated fragments, such as Bb, rather than native proteins. This precision enables potent blockade of the disease-driving AP while intentionally preserving the CP’s critical role in host defense and immune surveillance. Supported by a robust portfolio of intellectual property and promising Phase II data, NovelMed is advancing a differentiated pipeline of first-in-class biologics designed to achieve durable clinical outcomes without compromising the patient’s ability to fight infections. Strategic Partnership Opportunity Following the achievement of 100% transfusion avoidance in its Phase II monotherapy study and the recent regulatory clearance for SC administration, NovelMed is actively pursuing a strategic partnership to propel Ruxoprubart through late-stage global development. This program is exceptionally well-positioned for expansion, supported by U.S. FDA Orphan Drug Designation (ODD) and a validated, precision mechanism that addresses significant unmet needs in the PNH market. NovelMed seeks a partner with extensive clinical and commercial expertise to accelerate the regulatory path towards approval and support the global launch of this patient-friendly, self-administered therapy. By combining NovelMed’s innovative science with a partner's scale, the company aims to redefine the treatment landscape for rare complement-mediated diseases. Media Contact: Ya Gao, MS NovelMed Therapeutics, Inc. media@novelmed.com (216) 440 2696 Forward-Looking Statements This press release contains forward-looking statements that reflect NovelMed’s current expectations and projections about future events. Ruxoprubart (NM8074) is an investigational therapy and has not been approved by any regulatory authority for commercial use. The subcutaneous administration route has received regulatory clearance for further study; no subcutaneous clinical trials have been initiated. Forward-looking statements include expectations about clinical development, regulatory interactions, future study plans, and potential outcomes. NovelMed is a privately held, clinical stage biotechnology company which undertakes no obligation to update these statements except as required by law. A photo accompanying this announcement is available at

引言 重症肌无力（MG）是一种获得性神经‑肌肉接头传递障碍的自身免疫性疾病[1]，随着《中国重症肌无力诊断和治疗指南（2025 版）》的发布，MG 治疗理念迎来重要升级，指南明确提出「双达标」治疗目标；同时建议，条件允许的情况下启用快速起效疗法，以尽快实现治疗目标，并明确了难治性 MG 的定义[1]，为临床精准治疗提供了新方向。为此，丁香园特别邀请到了唐都医院神经内科副主任常婷教授，围绕 MG「双达标」治疗、难治性 MG 患者管理及补体 C5 抑制剂临床应用等主题进行学术解读。 问题一：《中国重症肌无力诊断和治疗指南（2025 版）》（以下简称「2025 版 MG 指南」）明确提出，MG 治疗目标为达到最小症状表达（MSE），即 MG-ADL 评分为 0 分或 1 分，同时治疗相关不良反应（CTCAE）级或泼尼松剂量为 5～10 mg/d。您如何解读这一目标的临床革新意义？ 常婷教授： 相比我国 2020 版 MG 指南中将治疗目标定义为「达到微小表现状态（MMS）或更好，CTCAE ≤ 1 级」，2025 版 MG 指南中推荐的治疗目标为「达到 MSE，即 MG-ADL 评分为 0 分或 1 分 ，同时 CTCAE ≤ 1 级或泼尼松剂量为 5～10 mg/d」[1]。这一修订旨在更好地指导临床实践操作，同时也反映出该领域最新研究进展： 2020 版 MG 指南中的 MMS，是指没有任何因肌无力引起的功能受限，经专科医师检查可发现某些肌肉无力。尽管 MMS 通常被作为主要治疗目标，但其无法量化的缺陷阻碍了对 MG 患者的客观评估，临床医生通常靠主观问询进行评估[1]。近年来，MG 随机对照试验或观察性研究将 MSE 作为治疗目标，可作为 MMS 的有效替代[1]。且 MSE 可通过 MG-ADL 评分为 0 分或 1 分进行量化评估，评估结果更易标准化，有助于临床医生在随访中快速识别患者是否达到治疗目标，并及时调整治疗方案[1]。 安全性方面，相比 2020 版 MG 指南，2025 版 MG 指南中将「泼尼松剂量为 5～10 mg/d」新增为治疗目标之一，主要是由于有研究观察到当泼尼松日剂量 ≤ 5 mg 时，MG 患者的整体生活质量可达到或优于 MMS 状态，对于健康相关生活质量量表评分有积极影响[1]。此外，将泼尼松剂量明确纳入治疗目标，是对长期激素治疗风险的积极应对，也为临床实践中激素的规范减量提供了明确依据。 此外，2025 版 MG 指南在治疗目标这一条推荐意见中还强调：若条件允许，建议启用快速起效疗法尽快实现治疗目标，这一建议具有重要的临床意义[1]。 问题二：近年来，补体系统激活被发现在 MG 的发病过程中发挥重要作用。请您结合既往试验数据及临床经验，谈谈补体 C5 抑制剂在实现更高 MG 治疗目标方面，有哪些临床特点？ 常婷教授： 依库珠单抗是一种靶向补体 C5 的人源化单克隆抗体，通过高亲和力特异性结合人类末端补体蛋白 C5，阻断 C5 裂解成 C5a 和 C5b，从而有效抑制 C5a 诱导的促炎细胞趋化性和 C5b 诱导的膜攻击复合物的形成[1]。 依库珠单抗治疗抗乙酰胆碱受体抗体阳性（AChR Ab+）全身型重症肌无力（gMG）成人患者 Ⅲ 期临床试验（REGAIN）结果显示，依库珠单抗治疗 1 周后即可观察到 MG-ADL 评分的改善[2]；治疗 26 周时，多项次要终点显示依库珠单抗组患者 MG-ADL 评分、MG 定量评分（QMG）、MG 复合量表（MGC）评分和 MG 相关生活质量 15 项（MG-QOL15）评分相比基线平均降低 4.2 分（P = 0.0058）、4.6 分（P = 0.0006）、8.1 分（P = 0.0134）、12.6 分（P = 0.0010）[2]。 REGAIN 研究 OLE 期数据显示，依库珠单抗治疗 AChR 抗体阳性难治性 gMG 第 26 周时的症状和生活质量改善可持续至 130 周[3]；且与安慰剂相比，接受依库珠单抗治疗的 AChR 抗体阳性 gMG 患者，gMG 加重发生率降低 65%（p = 0.0061）、急救治疗发生率降低 66%（p = 0.0105），MG 相关的住院治疗发生率降低 72%（p = 0.0228）[3]。 REGAIN 研究 OLE 期数据显示，首次达到 MM 状态且在 OLE 基线使用过免疫抑制剂的患者，糖皮质激素（CS）、硫唑嘌呤（AZA）、吗替麦考酚酯（MMF）的平均每日剂量分别减少 18.7%、26.0% 和 16.0%[4]；安全性数据显示，依库珠单抗中位暴露 22.7 个月，长期安全性及耐受性良好，常见不良事件（AE）是头痛（37.6%）和鼻咽炎（31.6%），未报告脑膜炎球菌感染病例[3]。临床应用中需注意，接受依库珠单抗治疗前至少 2 周需进行脑膜炎球菌疫苗接种；若疫苗接种之后未满 2 周即开始接受依库珠单抗治疗的患者，必须采用抗生素预防性治疗直至疫苗接种满 2 周[1]。 除依库珠单抗外，目前我国获批用于 MG 治疗的补体 C5 抑制剂还有瑞利珠单抗[1]。瑞利珠单抗是一种长效 C5 补体抑制剂，其作用机制与依库珠单抗类似，该药半衰期较长，将其维持给药期从依库珠单抗的 2 周延长至 8 周[5,6]。瑞利珠单抗治疗 AChR Ab+ gMG 成人患者的Ⅲ期临床试验 CHAMPION-MG 研究及其 OLE 长期随访数据显示： 患者用药 1 周后 MG-ADL 及 QMG 评分即可获得改善，中位时间 2.1 周 MG-ADL 评分降低 ≥ 2 分，中位时间 4.1 周改善 ≥ 3 分[7]； 治疗 138 周时，62.8% 的患者可将每日泼尼松用量控制于 10 mg 以下，表明其能有助于激素减量[8]。 在维持治疗方面，瑞利珠单抗治疗 164 周内，患者 MG-ADL 评分改善，至 164 周，88.1%（141/160 ）的患者实现了 ≥ 2 分的 MG-ADL 评分改善，其中 ，有 41.8% 的患者（59/141）达到 0 或 1 分的评分（即 MSE）[8]； 安全性数据显示，瑞利珠单抗中位暴露 759 天，长期安全性及耐受性良好，大多数 AE 为轻中度，未报告脑膜炎球菌感染病例[8]。 此外，zilucoplan 是由 15 个氨基酸组成的大环肽，在中国已递交上市申请。其具有双重作用机制，既可通过与 C5 结合，抑制末端补体级联反应的激活，又可有效地阻断膜攻击复合物的形成。在 AChR 抗体阳性的 gMG 患者中，zilucoplan 可快速显著降低 MG-ADL 评分，从治疗第 1 周起即可观察到 MG-ADL、QMG、MGC 和 MG-QOL15 评分的显著下降，且可维持到第 12 周，耐受性良好[1]。 问题三：据悉，除治疗目标升级外，2025 版 MG 指南还进一步扩大了难治性 MG 的定义。能否请您概述一下近年来难治性 MG 定义演变的历程？ 常婷教授： 难治性 MG 住院率、病死率、机械通气使用率更高，医疗花费更多[9]，一直以来都是 MG 临床治疗的重大挑战。然而，既往对于难治性 MG 尚无统一的标准。回顾 2016 年，MG 管理国际共识指南首次提出难治性 MG 是指「患者应用足剂量、足疗程的糖皮质激素和至少两种免疫抑制剂后，干预后状态（PIS）无变化或加重，症状持续或伴药物不良反应导致功能受限」[10]。2024 年我国难治性 gMG 诊断和治疗专家共识关于难治性 MG 的诊断条件中也再三强调了「足量足疗程使用至少 2 种常规免疫治疗药物」的先决条件[9]。而本次 2025 版 MG 指南的更新，进一步扩大了难治性 MG 的定义，将「①对常规免疫治疗药物反应欠佳；②不能耐受药物不良反应或有使用禁忌证；③或病情易反复，需要定期给予补救治疗，难以达到治疗目标」，定义为难治性 MG[1]。 问题四：结合临床经验，您认为对于难治性 MG 患者，决定其治疗升级策略的核心考量因素有哪些？应如何选择个体化的治疗方案？ 常婷教授： 难治性 MG 升级治疗方案的制定，应当以循证医学证据为基础，明确患者的抗体类型，并结合患者的具体病情、经济条件和个人意愿等因素共同决策[9]。 目前，依库珠单抗、利妥昔单抗及艾加莫徳等靶向生物制剂已被临床研究证实对 MG（包括难治性 AChR-MG、MuSK-MG 或抗体阴性 MG）有效且安全性良好，已被国外指南/共识推荐用于难治性 MG 的治疗。真实世界研究结果显示托珠单抗可改善难治性 MG 症状及减少激素剂量，且安全性良好。此外，胸腺切除术或 CAR‑T 细胞疗法也可改善难治性 MG 患者的症状，但仍需大样本临床研究证实[1]。 基于此，2025 版 MG 指南推荐[1]： 对于难治性 AChR‑MG，建议首选依库珠单抗（证据等级：Ⅰa 级，推荐等级：A 级），也可考虑艾加莫徳（证据等级：Ⅱb 级，推荐等级：B 级）、利妥昔单抗（证据等级：Ⅱa 级，推荐等级：B 级），托珠单抗（证据等级：Ⅱb 级，推荐等级：B 级）、胸腺切除（证据等级：Ⅳ 级，推荐等级：C 级）或 CAR‑T 细胞疗法。 对于难治性 MuSK‑MG、LRP4‑MG 或血清阴性 MG，优先选择利妥昔单抗治疗（证据等级：Ⅱa 级，推荐等级：B 级）。 对上述治疗均无效的难治性 MG，可考虑自体造血干细胞移植（证据等级：Ⅳ 级，推荐等级：C 级）、环磷酰胺（证据等级：Ⅱb 级，推荐等级：B 级）或硼替佐米（证据等级：Ⅳ 级，推荐等级：C 级）。 结  语 近年来，新型靶向药物尤其是补体 C5 抑制剂的发展，为 MG 患者实现治疗「双达标」提供了关键支持。此次常婷教授紧扣《中国重症肌无力诊断和治疗指南（2025 版）》更新要点，深入解读了 MSE「双达标」治疗目标的临床革新价值，阐述了依库珠单抗等补体 C5 抑制剂在快速起效、持续缓解症状、助力 MSE 达标及实现激素减量等方面的数据。这些兼具深度与实用性的见解，为广大临床医生把握 MG 诊疗新方向、优化难治性 MG 患者管理策略提供了重要指导。未来，期待更多临床专家携手探索，推动 MG 诊疗领域的创新发展，为更多 MG 患者带来长期获益。 专家简介 常婷 教授 唐都医院神经内科副主任 主任医师，教授，博士（后）导师 •「国家科技重大专项」首席专家； • 陕西中青年科技创新领军人才；陕西省科技创新团队带头人 • 中华医学会神经病学分会神经免疫学组 委员 • 中国医师协会神经内科医师分会神经肌肉病和电生理学组 委员 • 中国医师协会神经修复学专业委员会神经免疫学组 副组长 • 中国罕见病联盟重症肌无力协作组 副组长 • 陕西省医师协会神经内科医师分会 副会长 • 陕西重症肌无力专科联盟 组长 • 主持国家科技重大专项 1 项，国家重点研发计划课题 1 项，国家自然科学基金 4 项，国家重大疑难疾病中西医临床协作项目 1 项，陕西省重点课题 2 项；近 5 年以第一/通讯作者在 Cell、Science Translational Medicine、Med、Journal of Neuroinflammation 等期刊发表 SCI 论文 34 篇；执笔国家级指南 2 部；授权国家发明专利及软著 10 项 • 以第一及重要完成人获陕西省高校优秀成果特等奖、天津市自然科学一等奖、陕西省创新创业大赛一等奖 • 《中华神经科杂志》《中国神经免疫学和神经病学杂志》编委 ▲上下滑动查看▼ 所有使用依库珠单抗和瑞利珠单抗的患者必须接种四价脑膜炎疫苗（ACYW135），在有条件的情况下接种 B 型疫苗 声明：本文采访常婷教授并由常婷教授审校，内容由阿斯利康支持提供，仅供医疗卫生专业人士参考，不用于推广目的。 审批号：CN-178489，过期日期：2027-03-02 内容策划：杨娜 内容审核：张晓燕 题图来源：图虫创意 参考文献 [1]华医学会神经病学分会神经免疫学组 . 中国重症肌无力诊断和治疗指南（2025版）[J]. 中华神经科杂志, 2025, 58(7): 721-741. 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