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
發表在《歐洲心力衰竭雜誌》上的3期試驗結果確定了中胚細胞異基因細胞療法的關鍵目標群體
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
紐約，2024年12月2日（GLOBE NEWSWIRE）——炎症性疾病異基因細胞藥物的全球領導者Mesoblast Limited（納斯達克股票代碼：MSO；澳大利亞證券交易所股票代碼：MSB）今天宣佈在2024年11月在線出版的著名同行評審期刊（EJHF）上發表了一篇重要文章，該雜誌報道說，公司的異基因細胞療法Revascor進行了一次心肌注射 (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.
這項針對射血分數降低的慢性心力衰竭（HFref）患者的隨機對照Dream-HF試驗的結果表明，心血管死亡風險最高的對照組是缺血性病因和炎症的對照組，並顯示單次心肌內注射Mesoblast的間充質前體細胞療法（mPCs；rexlemestrocel-L）可持續降低這些患者的心血管死亡率高風險患者。這可以確定對REVASCOR療法有反應的靶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的首席研究員、德州心臟研究所醫學總監FACC醫學主任艾默生·佩林博士說：「Mesoblast的異基因MPC可以恢復受損、發炎的心臟中抗炎和促炎細胞因子之間的平衡。單次給藥 mPC 似乎足以改善高風險 HFref 炎症患者的存活率和其他主要臨床結果。這些效果是在針對神經激素失衡和充血的現有治療的基礎上看到的，這提供了一種僅靠標準護理無法實現的改善疾病的方法。」
The newly published results showed that over a mean follow-up of 30 months in the DREAM-HF trial:
最新公佈的結果顯示，在Dream-HF試驗的平均30個月隨訪中：
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.
預示對照組患者心血管死亡風險最大的因素是炎症（基線血漿高靈敏度C反應蛋白≥2 mg/L；p=0.003）和缺血性HFref病因（p=0.097），心血管死亡風險分別增加61％和38％。
無論使用血漿hsCRP還是血漿IL-6作爲炎症生物標誌物，單次心肌內注射MPC都會顯著降低HFref發炎患者的心血管死亡風險，分別降低80％（p=0.003）和60％（p=0.037）。
與對照組相比，缺血性HFref（n=303）患者的2點MACE（心臟病發作或中風）降低了57％（p=0.016），將缺血性HFref（n=303）患者的3點MACE（心血管死亡、心臟病發作、中風）降低了35％（p=0.049）。
與對照組相比，缺血性HFref和炎症患者（n=158）的MPC分別將2點和3點的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首席執行官西爾維烏·伊特斯庫博士說：「我們正在爲我們的STRO3-ImmunoSelect和工業生產的心力衰竭產品REVASCOR尋找潛在的批准途徑，涵蓋從兒科先天性心臟病到成人缺血性HFref的整個過程。」「今年早些時候，我們收到了美國食品藥品監督管理局（FDA）的反饋，該反饋爲使用左心室輔助裝置（LVAD）的終末期缺血HFref患者的加速批准途徑提供了支持。這份新出版物確定了較大的缺血性HFref人群，這些人群對REVASCOR有反應並具有死亡益處。」
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).
關於心臟病中的Revascor（rexlemestrocel-L）
REVASCOR是免疫選擇和培養擴大的間充質前體細胞（MPC）的異基因製劑，正在開發爲一種免疫調節療法，旨在解決從紐約心臟協會（NYHA）二級到末期疾病的HFref患者中存在的心臟和心血管系統高度炎症，以降低重大心血管事件和併發症的高發率。該研究性療法已在兩項針對慢性HFref患者的大型安慰劑對照隨機研究中進行了評估。其中包括一項針對537名NYHA II/III類治療患者（dream-HF）2的試驗，以及一項針對終末期HFref患者植入左心室輔助裝置（LVAD）的159名患者的試驗。
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擁有美國食品藥品監督管理局（FDA）再生醫學高級療法（RMAT）和孤兒藥名稱，適用於終末期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.
關於慢性心力衰竭
慢性心力衰竭（CHF）的特徵是心臟功能不佳，導致流向人體重要器官和四肢的血液不足。這種疾病影響了美國約650萬人，全球影響了2600萬人，患病率和發病率不斷上升。慢性心力衰竭患者通常根據患者的身體限制根據紐約心臟協會（NYHA）的類別進行分類。I 類（輕度）患者沒有限制，而 IV 類患者（嚴重/末期）即使在休息時也會出現症狀。
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.
隨着患者逐漸超過NYHA早期的II類疾病，同時心臟和血液循環中的炎症加劇，死亡率在5年時接近50％。3,4儘管最近批准了針對HFreF的新療法，但NYHA的II/III類HFref炎症患者仍然面臨心血管死亡、心臟病發作和中風的高風險。
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.
美國每年有超過10萬名患者發展爲終末期心力衰竭（NYHA三級/四級）。這些患者的一年死亡率超過 50%。5 在終末期心力衰竭患者中使用 LVAD 以提高存活率的勢頭正在增強，美國每年大約植入 2,000 個 LVAD 作爲目標療法，6 其中大多數具有缺血性病因。
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.
關於 Mesoblast
Mesoblast（公司）在開發用於治療嚴重和危及生命的炎症性疾病的異基因（現成）細胞藥物方面處於世界領先地位。該公司利用其專有的間充質譜系細胞療法技術平台建立了廣泛的後期候選產品組合，這些候選產品通過釋放抗炎因子來對抗和調節免疫系統的多個效應組來應對嚴重炎症，從而顯著減少破壞性炎症過程。
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擁有強大而廣泛的全球知識產權組合，所有主要市場的保護期至少可延至2041年。該公司的專有製造工藝可生產工業規模、冷凍保存、現成的細胞藥物。這些具有明確藥物釋放標準的細胞療法計劃隨時可供全球患者使用。
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正在基於其remestemcel-L和rexlemestrocel-L異基因基質細胞技術平台爲不同適應症開發候選產品。Remestemcel-L正在開發用於兒童和成人的炎症性疾病，包括類固醇難治性急性移植物抗宿主病和生物耐藥性炎症性腸病。Rexlemestrocel-L 正在開發用於晚期慢性心力衰竭和慢性下背痛。Mesoblast的被許可人已在日本和歐洲將兩種產品商業化，該公司已在歐洲和中國就某些第三階段資產建立了商業合作伙伴關係。
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在澳大利亞、美國和新加坡設有分支機構，並在澳大利亞證券交易所（MSB）和納斯達克（MESO）上市。欲了解更多信息，請參閱 LinkedIn：Mesoblast Limited 和 Twitter：@Mesoblast
References / Footnotes
參考文獻/腳註
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等人間充質前體細胞可降低伴有炎症的缺血性心力衰竭的死亡率和主要發病率：dream-HF。2024 年 Eur J 心力衰竭。
Perin EC。等人。心力衰竭患者靶向心內膜間充質前體細胞療法的隨機試驗。JACC 第 81 卷，第 9 號，2023 年。
AHA 的 2017 年心臟病和中風統計數據
Ponikowski P.，等心力衰竭：在全球範圍內預防疾病和死亡。歐洲心臟病學會。2014；1：4-25
古斯塔夫森 F，羅傑斯 JG。晚期心力衰竭的左心室輔助設備治療：患者選擇和預後。2017年歐洲心力衰竭雜誌；19:595-602。
Yuzefpolskaya m 等人。Ann Thorac Surg 2023; 115:311-28
