Isatuximab-IRFC

New Sarclisa subcutaneous formulation met co-primary endpoints in the IRAKLIA phase 3 study in multiple myeloma Sarclisa SC formulation added to Pd for the treatment of R/R MM met the co-primary endpoints in the IRAKLIA phase 3 study, demonstrating non-inferiority compared to Sarclisa IV IRAKLIA is the first global phase 3 study to evaluate the SC administration of a cancer treatment via an OBDS OBDS is an alternative delivery method designed to improve the patient experience and currently available SC administration January 9, 2025. Results from the investigational, randomized, open-label IRAKLIA phase 3 study demonstrated that Sarclisa administered at a fixed dose subcutaneously (SC) via an on-body delivery system (OBDS) in combination with pomalidomide and dexamethasone (Pd) met its co-primary endpoints of non-inferior objective response rate (ORR) and observed concentration before dosing (C trough) at steady state compared to intravenous (IV) Sarclisa administered at a weight-based dose in combination with Pd in patients with relapsed or refractory multiple myeloma (R/R MM). Key secondary endpoints, including very good partial response (VGPR), incidence rate of infusion reactions and C trough at cycle 2 were also achieved. The study is ongoing, and the full results will be presented at a forthcoming medical meeting. Sikander Ailawadhi, MD Professor of Medicine, Division of Hematology/Oncology at Mayo Clinic Florida and principal investigator of the study “The consistent overall response rate and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous Sarclisa represent an exciting advancement, offering insight into a potential new administration option for patients. The results from IRAKLIA, in patients with relapsed or refractory multiple myeloma, support the potential of an on-body delivery system to help ease the delivery of a new formulation without impacting patient outcomes.” The IRAKLIA study was conducted using Enable Injections’ enFuse® hands-free OBDS, which was designed to administer high-volume medicines subcutaneously through an automated drug delivery technology. The enFuse device leverages a hidden and retractable needle that is thinner compared to commonly used SC injection needles. Houman Ashrafian, MD, PhD Executive Vice President, Head of Research and Development at Sanofi “We are fueled by our focus on innovation and finding best-in-class solutions to help ease the burden of disease for patients. The IRAKLIA study results are a prime example of what’s driving our scientific engine. Being able to possibly bring a novel option that helps reduce time in a healthcare facility is driven by our patient and provider-centric mindset. We look forward to sharing full results and working to bring this new advancement to the multiple myeloma community.” Additional studies evaluating Sarclisa SC formulations across different combinations and lines of therapy are ongoing. The safety and efficacy of Sarclisa SC and the enFuse device have not been evaluated by any regulatory authority outside of their approved indications. Regulatory submissions in the US and in the EU are planned during the first half of 2025. IRAKLIA is a randomized, open-label, pivotal phase 3 study evaluating the non-inferiority of Sarclisa SC formulation administered at a fixed dose subcutaneously via an OBDS versus weight-based dosed Sarclisa IV in combination with Pd in adult patients with R/R MM. The study enrolled 531 patients across 252 global sites, who were equally randomized to receive Sarclisa SC or IV in combination with Pd for 28-day cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever came first. In the SC arm, Sarclisa was administered at a fixed dose SC weekly for four weeks during the first cycle and every two weeks for subsequent cycles. In the IV arm, Sarclisa was administered at a weight-based dose via IV infusion weekly for four weeks during the first cycle and every two weeks for subsequent cycles. The study enrolled adult patients with MM who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. The co-primary outcomes being assessed are ORR, defined as the proportion of patients with stringent complete response, complete response, VGPR, and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC), and observed C trough at steady state, defined as observed Sarclisa plasma concentrations. Based in the US (Cincinnati, Ohio), Enable Injections is a global healthcare innovation company committed to improving the patient treatment experience through the development and manufacturing of enFuse. enFuse is an innovative wearable drug delivery platform that is designed to deliver large volumes of pharmaceutical and biologic therapeutics via subcutaneous administration, with the aim of improving convenience, supporting superior outcomes, and advancing healthcare system economics. For more information, visit https://enableinjections.com. Sarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA. Currently, Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. Based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with Pd for the treatment of patients with R/R MM who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor, and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with R/R MM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is approved in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as a front-line treatment option for adult patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for autologous stem cell transplant (ASCT), based on the IMROZ phase 3 study. On November 14, 2024, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of Sarclisa-VRd in this patient population. A final decision is expected in the coming months. Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. Further clinical studies evaluating a subcutaneous administration method for Sarclisa are ongoing. In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat often rare cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers. We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. The content above comes from the network. if any infringement, please contact us to modify.

来源：药渡 撰文：西江鱼     编辑：维他命 2025年1月10日，康诺亚生物科技有限公司宣布与全球领先的生物制药公司Timberlyne Therapeutics达成了一项具有里程碑意义的独家授权许可协议。 根据协议，康诺亚自主研发的靶向CD38人源化单克隆抗体CM313将在全球范围内（不包括中国内地、香港、澳门及台湾地区）进行开发、生产及商业化。此次交易总额超过3.6亿美元，包括3000万美元的首付款及近期付款，以及基于未来销售及开发里程碑的最多3.375亿美元额外付款，外加销售净额的分层特许权使用费。这一合作不仅标志着康诺亚在创新药出海战略上的重大突破，更预示着CM313在全球医药市场中的巨大潜力。 图源：康诺亚公众号 01 原发免疫性血小板减少症 原发免疫性血小板减少症（ITP）是一种由免疫介导的血小板破坏过多和/或生成减少引起的出血性疾病。患者常表现为皮肤瘀斑、紫癜、牙龈出血、鼻出血等症状，严重时可发生颅内出血等危及生命的并发症。ITP的发病机制复杂，涉及多种免疫细胞和分子的异常活化，导致血小板生成减少和破坏增加。 原发免疫性血小板减少症（ITP）的传统疗法主要包括糖皮质激素治疗、静脉注射免疫球蛋白、脾切除以及使用促血小板生成药物等。然而，这些疗法存在诸多局限： 糖皮质激素虽能迅速提升血小板计数，但长期应用易导致骨质疏松、高血压、糖尿病等副作用； 免疫球蛋白的静脉注射虽然能带来短暂的治疗效果，但由于其高昂的价格，并不适宜作为长期的治疗方案； 另一方面，脾切除手术虽然能让部分患者实现长期的病情缓解，但手术本身伴随着高风险，并且在手术后，患者容易遭遇感染、血栓形成等多种并发症； 促血小板生成药物虽能刺激血小板生成，但停药会出现易复发的现象，且部分患者对药物有不敏感的情况。 因此，开发新的、更有效的治疗方法成为ITP治疗领域亟待解决的问题。近年来，随着对ITP发病机制研究的深入，越来越多的新型疗法被开发出来，其中就包括靶向CD38的单克隆抗体CM313。 02 CM313的作用机制 CM313是康诺亚自主研发的靶向CD38的人源化单克隆抗体，具有独特的作用机制和显著的治疗优势。CD38是一种多功能酶和细胞表面受体，在T细胞、B细胞、NK细胞等免疫细胞中广泛表达，参与细胞增殖、活化、分化及凋亡等过程。在ITP患者中，CD38阳性长寿命浆细胞（LLPC）能够持续产生致病性抗体，导致血小板破坏增加和生成减少。 CM313通过特异性地结合CD38分子，能够清除包括LLPC在内的抗体分泌细胞，从而阻断抗体介导的血小板破坏，恢复血小板的正常生成和功能。此外，CM313还能抑制单核巨噬细胞系统介导的抗体依赖性细胞毒性作用，进一步减少血小板的破坏。这一机制使得CM313能够快速、持久地提升患者血小板计数，降低出血风险。 03 CM313临床数据几何？ CM313在治疗成人原发免疫性血小板减少症的临床研究中取得了很好的结果。一项由研究者发起的单臂、开放性1/2期临床研究纳入了22例ITP患者，评估了CM313的安全性和有效性。患者接受每周一次的CM313治疗（16mg/kg），共计8周，随后进入16周的观察随访期。 研究结果显示，CM313能够快速、持久地提升患者血小板计数，降低出血风险。在8周的治疗期间，95.5%的患者实现了血小板计数≥50×10^9/L的缓解标准，且血小板计数首次达到该水平的中位时间仅为1周。第8周时，总有效率为81.8%，第12周时为86.4%，第24周时为63.6%。中位累积缓解持续时间为23周，显示出CM313的持久疗效。 在安全性评估方面，CM313治疗并未引发与治疗直接相关的严重不良事件。其中，最常见的与治疗相关的不良事件为输液时产生的反应以及上呼吸道感染，且这些事件主要以轻度或中度为主。这些不良反应均可通过暂时中断输注和给予糖皮质激素后得到缓解，未对患者的治疗造成严重影响。此外，CM313在治疗过程中未观察到明显的免疫抑制或感染风险增加，进一步证明了其良好的安全性和耐受性。 除了ITP外，CM313在治疗复发/难治性多发性骨髓瘤及淋巴瘤中的初步有效性也为其在更广泛适应症中的应用提供了可能。这些临床数据的公布，进一步增强了业界对CM313的信心和期待，为其在全球市场的推广和应用奠定了坚实基础。 04 CD38单抗赛道潜力及现状 CD38单抗作为治疗自身免疫性疾病和恶性肿瘤的重要靶点之一，近年来受到了广泛关注。从市场价值来看，CD38单抗赛道具有巨大的发展潜力。随着全球人口老龄化趋势的加剧和自身免疫性疾病、恶性肿瘤发病率的上升，对CD38单抗等创新药物的需求将持续增长。据市场研究机构预测，到2030年，全球CD38单抗市场规模将达到数十亿美元以上。因此，CM313的出海不仅为康诺亚带来了广阔的市场空间，也为整个CD38单抗赛道的发展注入了新的活力。 目前，全球已有两款CD38单抗获批上市，分别是强生的达雷妥尤单抗（Daratumumab）和赛诺菲的伊沙妥昔单抗（Isatuximab），主要用于治疗多发性骨髓瘤。纵观国产CD38单抗新药的研发现状，目前已有6款药物进入临床试验阶段，其中进展最为迅速的是尚健生物的SG301，已成功迈入临床III期；紧随其后的是康诺亚的CM313，也已进入临床II期阶段。 康诺亚与Timberlyne Therapeutics的合作标志着CM313正式出海，进入全球市场。这一合作不仅为康诺亚带来了可观的经济回报，更重要的是，它展示了中国创新药企在全球医药市场中的竞争力和影响力。通过与国际知名药企的合作，康诺亚能够借助对方的研发、生产和商业化能力，加速CM313在全球市场的推广和应用，为全球患者提供更多、更好的治疗选择。 在国内，NewCo模式也逐渐被一些创新药企采纳。除了康诺亚外，还有多家创新药企正在积极探索和实践NewCo模式。例如，恒瑞医药、百济神州、信达生物等知名企业都在通过加大研发投入、拓展国际合作等方式，不断提升自身的创新能力和市场竞争力。通过这一模式，企业可以更加高效地利用全球资源，加速新药研发进程，提高产品质量和疗效，从而在全球市场中占据一席之地。同时，NewCo模式也有助于推动中国医药产业的转型升级，提升整个行业的创新能力和国际竞争力。 结 语 康诺亚CD38单抗CM313的出海合作，是中国创新药企在国际市场上取得的一次重要突破。通过与海外药企的合作，CM313有望在全球范围内实现更广泛的应用和推广，并成为复发/难治性多发性骨髓瘤，以及系统性红斑狼疮、原发免疫性血小板减少症等自身免疫性疾病的创新型治疗选择。 参考文献： 1. 康诺亚公司官网 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 君实PD-1特瑞普利单抗的「华丽蜕变」：由“附条件批准”迈向“常规批准” A股医药股即将吹响反攻号角？2024年涨幅&市值TOP20全盘点 国内首款！男性HPV疫苗正式获批，默沙东搅动市场风云