Revascor Improves Survival and Reduces Major Morbidity in High-Risk Ischemic Heart Failure Patients With Inflammation
Revascor Improves Survival and Reduces Major Morbidity in High-Risk Ischemic Heart Failure Patients With Inflammation
DREAM-HF's lead investigator, Dr. Emerson C. Perin, MD, PhD, FACC, Medical Director at The Texas Heart Institute, said, "Mesoblast's allogeneic MPCs may restore the balance between anti-inflammatory and pro-inflammatory cytokines in the damaged, inflamed heart. A single administration of MPCs appears sufficient to improve survival and other major clinical outcomes in high-risk HFrEF patients with inflammation. These effects are seen on top of existing treatments that target neurohormonal imbalances and congestion, providing a disease-modifying approach not achievable with standard-of-care alone."Phase 3 trial results published in European Journal of Heart Failure identify key target population for Mesoblast allogeneic cell therapy
发表在《欧洲心力衰竭杂志》上的3期试验结果确定了中胚细胞异基因细胞疗法的关键目标群体
NEW YORK, Dec. 02, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced a key publication in the November 2024 online issue of the prestigious peer-reviewed European Journal of Heart Failure (EJHF), which reports that a single intramyocardial injection of the Company's allogeneic cell therapy Revascor (rexlemestrocel-L) results in improved survival in high-risk patients with ischemic heart failure and inflammation.1
纽约，2024年12月2日（GLOBE NEWSWIRE）——炎症性疾病异基因细胞药物的全球领导者Mesoblast Limited（纳斯达克股票代码：MSO；澳大利亚证券交易所股票代码：MSB）今天宣布在2024年11月在线出版的著名同行评审期刊（EJHF）上发表了一篇重要文章，该杂志报道说，公司的异基因细胞疗法Revascor进行了一次心肌注射 (rexlemestrocel-L) 可提高缺血性心力衰竭和炎症的高危患者的存活率。1
Results from the randomized, controlled DREAM-HF trial in patients with chronic heart failure with reduced ejection fraction (HFrEF) identified the control group at highest risk of cardiovascular death as being those with ischemic etiology and inflammation and showed that a single intramyocardial injection of Mesoblast's mesenchymal precursor cell therapy (MPCs; rexlemestrocel-L) resulted in a sustained reduction in cardiovascular mortality in these high-risk patients. This identifies the target HFrEF population that is responsive to REVASCOR therapy.
这项针对射血分数降低的慢性心力衰竭（HFref）患者的随机对照Dream-HF试验的结果表明，心血管死亡风险最高的对照组是缺血性病因和炎症的对照组，并显示单次心肌内注射Mesoblast的间充质前体细胞疗法（mPCs；rexlemestrocel-L）可持续降低这些患者的心血管死亡率高风险患者。这可以确定对REVASCOR疗法有反应的靶HFref人群。
DREAM-HF's lead investigator, Dr. Emerson C. Perin, MD, PhD, FACC, Medical Director at The Texas Heart Institute, said, "Mesoblast's allogeneic MPCs may restore the balance between anti-inflammatory and pro-inflammatory cytokines in the damaged, inflamed heart. A single administration of MPCs appears sufficient to improve survival and other major clinical outcomes in high-risk HFrEF patients with inflammation. These effects are seen on top of existing treatments that target neurohormonal imbalances and congestion, providing a disease-modifying approach not achievable with standard-of-care alone."
Dream-HF的首席研究员、德州心脏研究所医学总监FACC医学主任艾默生·佩林博士说：“Mesoblast的异基因MPC可以恢复受损、发炎的心脏中抗炎和促炎细胞因子之间的平衡。单次给药 mPC 似乎足以改善高风险 HFref 炎症患者的存活率和其他主要临床结果。这些效果是在针对神经激素失衡和充血的现有治疗的基础上看到的，这提供了一种仅靠标准护理无法实现的改善疾病的方法。”
The newly published results showed that over a mean follow-up of 30 months in the DREAM-HF trial:
最新公布的结果显示，在Dream-HF试验的平均30个月随访中：
Factors portending the greatest risk for cardiovascular death in control patients were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; p=0.003) and ischemic HFrEF etiology (p=0.097), with increased cardiovascular death risk of 61% and 38%, respectively.
A single intra-myocardial MPC administration significantly lowered the risk of cardiovascular death in HFrEF patients with inflammation regardless of whether plasma hsCRP or plasma IL-6 was used as inflammatory biomarker by 80% (p=0.003) and 60% (p=0.037) respectively.
MPCs reduced 2-point MACE (heart attack or stroke) by 57% (p=0.016) and 3-point MACE (cardiovascular death, heart attack, stroke) by 35% (p=0.049) in patients with ischemic HFrEF (n=303) compared to controls.
MPCs reduced 2-point and 3-point MACE by 88% (p=0.005) and 52% (p=0.018) respectively, in patients with ischemic HFrEF and inflammation (n=158) compared to controls.
预示对照组患者心血管死亡风险最大的因素是炎症（基线血浆高灵敏度C反应蛋白≥2 mg/L；p=0.003）和缺血性HFref病因（p=0.097），心血管死亡风险分别增加61％和38％。
无论使用血浆hsCRP还是血浆IL-6作为炎症生物标志物，单次心肌内注射MPC都会显著降低HFref发炎患者的心血管死亡风险，分别降低80％（p=0.003）和60％（p=0.037）。
与对照组相比，缺血性HFref（n=303）患者的2点MACE（心脏病发作或中风）降低了57％（p=0.016），将缺血性HFref（n=303）患者的3点MACE（心血管死亡、心脏病发作、中风）降低了35％（p=0.049）。
与对照组相比，缺血性HFref和炎症患者（n=158）的MPC分别将2点和3点的MACE降低了88％（p=0.005）和52％（p = 0.018）。
"We are pursuing potential approval pathways for our STRO3-immunoselected and industrially manufactured heart failure product REVASCOR across the continuum from pediatric congenital heart disease to adults with ischemic HFrEF," said Mesoblast Chief Executive Dr. Silviu Itescu. "Earlier this year we received feedback from the U.S. Food and Drug Administration (FDA) providing support for an accelerated approval pathway in end-stage ischemic HFrEF patients with a left ventricular assist device (LVAD). This new publication identifies the larger ischemic HFrEF population which responds to REVASCOR with mortality benefit."
Mesoblast首席执行官西尔维乌·伊特斯库博士说：“我们正在为我们的STRO3-ImmunoSelect和工业生产的心力衰竭产品REVASCOR寻找潜在的批准途径，涵盖从儿科先天性心脏病到成人缺血性HFref的整个过程。”“今年早些时候，我们收到了美国食品药品监督管理局（FDA）的反馈，该反馈为使用左心室辅助装置（LVAD）的终末期缺血HFref患者的加速批准途径提供了支持。这份新出版物确定了较大的缺血性HFref人群，这些人群对REVASCOR有反应并具有死亡益处。”
About Revascor (rexlemestrocel-L) in Heart Disease
REVASCOR is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells (MPC) and is being developed as an immunomodulatory therapy to address the high degree of inflammation in the heart and cardiovascular system that is present across the spectrum of HFrEF patients ranging from New York Heart Association (NYHA) class II through end-stage disease, in order to reduce the high rate of major cardiovascular events and complications. This investigational therapy has been evaluated in two large placebo-controlled randomized studies in patients with chronic HFrEF. These consisted of a trial with 537 NYHA class II/III treated patients (DREAM-HF)2 and a 159-patient trial in end-stage HFrEF patients implanted with a left ventricular assist device (LVAD).
关于心脏病中的Revascor（rexlemestrocel-L）
REVASCOR是免疫选择和培养扩大的间充质前体细胞（MPC）的异基因制剂，正在开发为一种免疫调节疗法，旨在解决从纽约心脏协会（NYHA）二级到末期疾病的HFref患者中存在的心脏和心血管系统高度炎症，以降低重大心血管事件和并发症的高发率。该研究性疗法已在两项针对慢性HFref患者的大型安慰剂对照随机研究中进行了评估。其中包括一项针对537名NYHA II/III类治疗患者（dream-HF）2的试验，以及一项针对终末期HFref患者植入左心室辅助装置（LVAD）的159名患者的试验。
Rexlemestrocel-L has US Food and Drug Administration (FDA) Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations for patients with end-stage HFrEF implanted with an LVAD.
Rexlemestrocel-L拥有美国食品药品监督管理局（FDA）再生医学高级疗法（RMAT）和孤儿药名称，适用于终末期HFref植入LVAD的患者。
About Chronic Heart Failure
Chronic heart failure (CHF) is characterized by poor heart function resulting in insufficient blood flow to the body's vital organs and extremities. This condition affects approximately 6.5 million people in the United States and 26 million people globally with increasing prevalence and incidence. Chronic heart failure patients are commonly classified according to the New York Heart Association (NYHA) categories based on the patient's physical limitations. Class I (mild) patients have no limitations while Class IV patients (severe/end stage) experience symptoms even at rest.
关于慢性心力衰竭
慢性心力衰竭（CHF）的特征是心脏功能不佳，导致流向人体重要器官和四肢的血液不足。这种疾病影响了美国约650万人，全球影响了2600万人，患病率和发病率不断上升。慢性心力衰竭患者通常根据患者的身体限制根据纽约心脏协会（NYHA）的类别进行分类。I 类（轻度）患者没有限制，而 IV 类患者（严重/末期）即使在休息时也会出现症状。
The mortality rate approaches 50% at 5 years as patients progress beyond NYHA early class II disease in parallel with increasing inflammation in the heart and in the circulation.3,4 Despite recent approvals of new therapies for HFrEF, NYHA class II/III HFrEF patients with inflammation remain at high risk for cardiovascular death, heart attacks and strokes.
随着患者逐渐超过NYHA早期的II类疾病，同时心脏和血液循环中的炎症加剧，死亡率在5年时接近50％。3,4尽管最近批准了针对HFreF的新疗法，但NYHA的II/III类HFref炎症患者仍然面临心血管死亡、心脏病发作和中风的高风险。
Over 100,000 patients annually in the US progress to end-stage heart failure (NYHA class IIIB/IV). These patients have a one-year mortality exceeding 50%.5 Use of LVADs in end-stage heart failure patients to improve survival is gaining momentum, with approximately 2,000 LVADs implanted as destination therapy annually in the US,6 the majority of whom have an ischemic etiology.
美国每年有超过10万名患者发展为终末期心力衰竭（NYHA三级/四级）。这些患者的一年死亡率超过 50%。5 在终末期心力衰竭患者中使用 LVAD 以提高存活率的势头正在增强，美国每年大约植入 2,000 个 LVAD 作为目标疗法，6 其中大多数具有缺血性病因。
About Mesoblast
Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process.
关于 Mesoblast
Mesoblast（公司）在开发用于治疗严重和危及生命的炎症性疾病的异基因（现成）细胞药物方面处于世界领先地位。该公司利用其专有的间充质谱系细胞疗法技术平台建立了广泛的后期候选产品组合，这些候选产品通过释放抗炎因子来对抗和调节免疫系统的多个效应组来应对严重炎症，从而显著减少破坏性炎症过程。
Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company's proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.
Mesoblast拥有强大而广泛的全球知识产权组合，所有主要市场的保护期至少可延至2041年。该公司的专有制造工艺可生产工业规模、冷冻保存、现成的细胞药物。这些具有明确药物释放标准的细胞疗法计划随时可供全球患者使用。
Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, and biologic-resistant inflammatory bowel disease. Rexlemestrocel-L is being developed for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast's licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.
Mesoblast正在基于其remestemcel-L和rexlemestrocel-L异基因基质细胞技术平台为不同适应症开发候选产品。Remestemcel-L正在开发用于儿童和成人的炎症性疾病，包括类固醇难治性急性移植物抗宿主病和生物耐药性炎症性肠病。Rexlemestrocel-L 正在开发用于晚期慢性心力衰竭和慢性下背痛。Mesoblast的被许可人已在日本和欧洲将两种产品商业化，该公司已在欧洲和中国就某些第三阶段资产建立了商业合作伙伴关系。
Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see , LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
Mesoblast在澳大利亚、美国和新加坡设有分支机构，并在澳大利亚证券交易所（MSB）和纳斯达克（MESO）上市。欲了解更多信息，请参阅 LinkedIn：Mesoblast Limited 和 Twitter：@Mesoblast
References / Footnotes
参考文献/脚注
Perin EC. Et al. Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF. Eur J Heart Fail 2024.
Perin EC. Et al. Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients with Heart Failure. JACC Vol. 81, No. 9, 2023.
AHA's 2017 Heart Disease and Stroke Statistics
Ponikowski P., et al. Heart Failure: Preventing disease and death worldwide. European Society of Cardiology. 2014; 1: 4-25
Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes. European Journal of Heart Failure 2017;19:595-602.
Yuzefpolskaya M et al. Ann Thorac Surg 2023; 115:311-28
Perin EC等人间充质前体细胞可降低伴有炎症的缺血性心力衰竭的死亡率和主要发病率：dream-HF。2024 年 Eur J 心力衰竭。
Perin EC。等人。心力衰竭患者靶向心内膜间充质前体细胞疗法的随机试验。JACC 第 81 卷，第 9 号，2023 年。
AHA 的 2017 年心脏病和中风统计数据
Ponikowski P.，等心力衰竭：在全球范围内预防疾病和死亡。欧洲心脏病学会。2014；1：4-25
古斯塔夫森 F，罗杰斯 JG。晚期心力衰竭的左心室辅助设备治疗：患者选择和预后。2017年欧洲心力衰竭杂志；19:595-602。
Yuzefpolskaya m 等人。Ann Thorac Surg 2023; 115:311-28
