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
《歐洲心力衰竭雜誌》發表的三期試驗結果確定了mesoblast同種異體電芯治療的關鍵目標人群
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
紐約，2024年12月2日（全球新聞通訊）-- mesoblast有限公司（納斯達克：MESO；澳洲證券交易所：MSB），全球領導者在治療炎症疾病的同種異體細胞藥物，今天宣佈在2024年11月的《歐洲心力衰竭雜誌》（EJHF）線上期刊上發表了一項重要文章，報道公司同種異體電芯治療Revascor（rexlemestrocel-L）的單次心肌內注射在高風險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.
來自DREAm-HF隨機對照試驗的結果顯示，心臟射血分數降低型慢性心力衰竭（HFrEF）患者中，控制組的心血管死亡最高風險群體爲缺血性病因和炎症患者，並且單次心肌內注射mesoblast的間充質前電芯治療（MPCs；rexlemestrocel-L）導致這些高風險患者的心血管死亡率持續減少。這確認了對REVASCOR治療反應的HFrEF目標人群。
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，德克薩斯心臟研究所醫療主任Emerson C. Perin博士表示，"mesoblast的同種異體MPCs可能恢復受損和炎症心臟中抗炎和促炎細胞因子之間的平衡。單次給予MPCs似乎足以改善高風險HFrEF患者的生存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基礎上觀察到的，提供了一種無法僅通過標準護理實現的疾病修正方法。”
The newly published results showed that over a mean follow-up of 30 months in the DREAM-HF trial:
新發布的結果顯示，在DREAm-HF試驗平均隨訪30個月期間：
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風險最大的因素是炎症（基線血漿高敏感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了61%和38%。
單次心內電芯的給藥顯著降低了炎症狀態下HFrEF患者的心血管死亡風險，使用血漿hsCRP或血漿IL-6作爲炎症生物標誌物的情況下，分別降低了80%（p=0.003）和60%（p=0.037）。
與對照組相比，電芯在缺血性HFrEF患者（n=303）中將2點MACE（心臟病發作或中風）降低了57%（p=0.016），將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，電芯在有炎症的缺血性HFrEF患者（n=158）中將2點和3點MACE分別降低了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."
「我們正在追求STRO3免疫選擇和工業製造的心力衰竭產品REVASCOR的潛在批准路徑，從兒童先天性心臟病到缺血性HFrEF成人，」Mesoblast首席執行官Silviu Itescu博士說。「今年早些時候，我們收到美國食品和藥物管理局（FDA）的反饋，爲終末期缺血性HFrEF患者提供了加速批准路徑的支持，他們配備了左心室輔助裝置（LVAD）。這份新出版物確定了對REVASCOR反應良好的更大缺血性HFrEF人群，並帶來了生存受益。」
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).
關於心臟病中的Revascor（rexlemestrocel-L）
REVASCOR是一種異體準備的免疫選擇和培養擴展的間充質前體細胞（MPC），作爲一種免疫調節療法正在開發，旨在解決HFrEF患者心臟和心血管系統中的高炎症狀態，這些患者從紐約心臟協會（NYHA）II級到終末期疾病不等，以減少重大心血管事件和併發症的高發生率。這種實驗性療法在兩項大規模的安慰劑對照隨機研究中進行了評估，參與者爲慢性HFrEF患者。這些研究包括537名NYHA II/III級的治療患者（DREAm-HF）和159名植入了左心室輔助裝置（LVAD）的終末期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獲得了美國食品和藥物管理局（FDA）的再生醫學先進療法（RMAT）和孤兒藥物認證，用於終末期HFrEF患者植入LVAD的治療。
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）以心臟功能不全爲特徵，導致對身體重要器官和肢體的血液供應不足。該病症影響了大約650萬人在美國和2600萬人在全球，且發病率和患病率持續上升。慢性心力衰竭患者通常根據紐約心臟協會（NYHA）的分類依據患者的身體限制進行分類。I級（輕度）患者沒有任何限制，而IV級患者（重度/終末期）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.
隨着患者的病情從NYHA早期II級疾病進展，死亡率在5年內接近50%，同時心臟和循環系統內的炎症增加。儘管最近批准了一些新的HFrEF療法，NYHA II/III級HFrEF患者仍面臨心血管死亡、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.
每年在美國有超過100,000名患者進展到終末期心力衰竭（NYHA III級/IV級）。這些患者的一年死亡率超過50%。LVAD在終末期心力衰竭患者中的使用以提高生存率正在逐漸受到重視，每年在美國大約有2,000個LVAD作爲目的治療被植入，其中大多數患者有缺血性病因。
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.
關於mesoblast
mesoblast（公司）是開發異體（現貨）細胞藥物以治療嚴重和危及生命的炎症病症的全球領先者。該公司利用其專有的間充質譜系細胞療法技術平台，建立了一個廣泛的晚期產品候選組合，這些產品通過釋放抗炎因子來響應嚴重炎症，這些因子可以抵消和調節免疫系統的多個效應臂，從而顯著減少有害的炎症過程。
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，保護期至少延續到2041年，覆蓋所有主要市場。公司的專有製造工藝能夠實現工業規模的冷凍保存即用型電芯藥物。這些電芯治療產品具備明確的藥品發佈標準，計劃讓全球患者輕鬆獲得。
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正在基於其remestemcel-L和rexlemestrocel-L同種異體間充質幹細胞科技平台開發不同適應症的產品候選。remestemcel-L正在開發用於兒童和成人的炎症性疾病，包括類固醇抵抗性急性移植物抗宿主病和生物製劑抵抗性炎症性腸病。rexlemestrocel-L則用於治療高級慢性心力衰竭和慢性腰痛。兩款產品已在日本和歐洲由mesoblast的許可方商業化，公司在歐洲和中國爲某些3期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在澳洲、美國和新加坡設有辦事處，並在澳大利亞證券交易所（MSB）和納斯達克（MESO）上市。有關更多信息，請查看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。間充質前體細胞減少缺血性心力衰竭中的死亡率和重大發病率：DREAm-HF。eur j heart fail 2024。
Perin EC 等。心力衰竭患者靶向經內膜間充質前體細胞治療的隨機試驗。JACC第81卷，第9期，2023年。
美國心臟協會2017年心臟病和中風統計數據
Ponikowski P. 等。心力衰竭：全球範圍內預防疾病和死亡。歐洲心臟病學會。2014；1：4-25
Gustafsson F, 羅傑斯 JG. 在愛文思控股心力衰竭中的左心室輔助裝置治療：患者選擇和結果。《歐洲心力衰竭雜誌》2017;19:595-602。
Yuzefpolskaya 中單 等人. 《胸外科年鑑》2023; 115:311-28
譯文內容由第三人軟體翻譯。
