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
《欧洲心力衰竭杂志》发表的三期试验结果确定了mesoblast同种异体电芯治疗的关键目标人群
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（全球新闻通讯）-- mesoblast有限公司（纳斯达克：MESO；澳洲证券交易所：MSB），全球领导者在治疗炎症疾病的同种异体细胞药物，今天宣布在2024年11月的《欧洲心力衰竭杂志》（EJHF）线上期刊上发表了一项重要文章，报道公司同种异体电芯治疗Revascor（rexlemestrocel-L）的单次心肌内注射在高风险缺血性心力衰竭和炎症患者中改善生存率。
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.
来自DREAm-HF随机对照试验的结果显示，心脏射血分数降低型慢性心力衰竭（HFrEF）患者中，控制组的心血管死亡最高风险群体为缺血性病因和炎症患者，并且单次心肌内注射mesoblast的间充质前电芯治疗（MPCs；rexlemestrocel-L）导致这些高风险患者的心血管死亡率持续减少。这确认了对REVASCOR治疗反应的HFrEF目标人群。
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，德克萨斯心脏研究所医疗主任Emerson C. Perin博士表示，"mesoblast的同种异体MPCs可能恢复受损和炎症心脏中抗炎和促炎细胞因子之间的平衡。单次给予MPCs似乎足以改善高风险HFrEF患者的生存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基础上观察到的，提供了一种无法仅通过标准护理实现的疾病修正方法。”
The newly published results showed that over a mean follow-up of 30 months in the DREAM-HF trial:
新发布的结果显示，在DREAm-HF试验平均随访30个月期间：
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.
控制患者心血管死亡风险最大的因素是炎症（基线血浆高敏感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了61%和38%。
单次心内电芯的给药显著降低了炎症状态下HFrEF患者的心血管死亡风险，使用血浆hsCRP或血浆IL-6作为炎症生物标志物的情况下，分别降低了80%（p=0.003）和60%（p=0.037）。
与对照组相比，电芯在缺血性HFrEF患者（n=303）中将2点MACE（心脏病发作或中风）降低了57%（p=0.016），将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，电芯在有炎症的缺血性HFrEF患者（n=158）中将2点和3点MACE分别降低了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."
“我们正在追求STRO3免疫选择和工业制造的心力衰竭产品REVASCOR的潜在批准路径，从儿童先天性心脏病到缺血性HFrEF成人，”Mesoblast首席执行官Silviu Itescu博士说。“今年早些时候，我们收到美国食品和药物管理局（FDA）的反馈，为终末期缺血性HFrEF患者提供了加速批准路径的支持，他们配备了左心室辅助装置（LVAD）。这份新出版物确定了对REVASCOR反应良好的更大缺血性HFrEF人群，并带来了生存受益。”
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是一种异体准备的免疫选择和培养扩展的间充质前体细胞（MPC），作为一种免疫调节疗法正在开发，旨在解决HFrEF患者心脏和心血管系统中的高炎症状态，这些患者从纽约心脏协会（NYHA）II级到终末期疾病不等，以减少重大心血管事件和并发症的高发生率。这种实验性疗法在两项大规模的安慰剂对照随机研究中进行了评估，参与者为慢性HFrEF患者。这些研究包括537名NYHA II/III级的治疗患者（DREAm-HF）和159名植入了左心室辅助装置（LVAD）的终末期HFrEF患者。
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获得了美国食品和药物管理局（FDA）的再生医学先进疗法（RMAT）和孤儿药物认证，用于终末期HFrEF患者植入LVAD的治疗。
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）以心脏功能不全为特征，导致对身体重要器官和肢体的血液供应不足。该病症影响了大约650万人在美国和2600万人在全球，且发病率和患病率持续上升。慢性心力衰竭患者通常根据纽约心脏协会（NYHA）的分类依据患者的身体限制进行分类。I级（轻度）患者没有任何限制，而IV级患者（重度/终末期）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.
随着患者的病情从NYHA早期II级疾病进展，死亡率在5年内接近50%，同时心脏和循环系统内的炎症增加。尽管最近批准了一些新的HFrEF疗法，NYHA II/III级HFrEF患者仍面临心血管死亡、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.
每年在美国有超过100,000名患者进展到终末期心力衰竭（NYHA III级/IV级）。这些患者的一年死亡率超过50%。LVAD在终末期心力衰竭患者中的使用以提高生存率正在逐渐受到重视，每年在美国大约有2,000个LVAD作为目的治疗被植入，其中大多数患者有缺血性病因。
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）是开发异体（现货）细胞药物以治疗严重和危及生命的炎症病症的全球领先者。该公司利用其专有的间充质谱系细胞疗法技术平台，建立了一个广泛的晚期产品候选组合，这些产品通过释放抗炎因子来响应严重炎症，这些因子可以抵消和调节免疫系统的多个效应臂，从而显著减少有害的炎症过程。
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，保护期至少延续到2041年，覆盖所有主要市场。公司的专有制造工艺能够实现工业规模的冷冻保存即用型电芯药物。这些电芯治疗产品具备明确的药品发布标准，计划让全球患者轻松获得。
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同种异体间充质干细胞科技平台开发不同适应症的产品候选。remestemcel-L正在开发用于儿童和成人的炎症性疾病，包括类固醇抵抗性急性移植物抗宿主病和生物制剂抵抗性炎症性肠病。rexlemestrocel-L则用于治疗高级慢性心力衰竭和慢性腰痛。两款产品已在日本和欧洲由mesoblast的许可方商业化，公司在欧洲和中国为某些3期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在澳洲、美国和新加坡设有办事处，并在澳大利亚证券交易所（MSB）和纳斯达克（MESO）上市。有关更多信息，请查看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。间充质前体细胞减少缺血性心力衰竭中的死亡率和重大发病率：DREAm-HF。eur j heart fail 2024。
Perin EC 等。心力衰竭患者靶向经内膜间充质前体细胞治疗的随机试验。JACC第81卷，第9期，2023年。
美国心脏协会2017年心脏病和中风统计数据
Ponikowski P. 等。心力衰竭：全球范围内预防疾病和死亡。欧洲心脏病学会。2014；1：4-25
Gustafsson F, 罗杰斯 JG. 在爱文思控股心力衰竭中的左心室辅助装置治疗：患者选择和结果。《欧洲心力衰竭杂志》2017;19:595-602。
Yuzefpolskaya 中单 等人. 《胸外科年鉴》2023; 115:311-28
译文内容由第三方软件翻译。
