Revascor Improves Survival and Reduces Major Morbidity in High-Risk Ischemic Heart Failure Patients With Inflammation
Mesoblast announced significant results from their Phase 3 DREAM-HF trial, published in the European Journal of Heart Failure. The study showed that a single intramyocardial injection of Revascor (rexlemestrocel-L) improved survival in high-risk patients with ischemic heart failure and inflammation. The therapy reduced cardiovascular death risk by 80% in patients with inflammation and reduced major adverse cardiovascular events (MACE) by 88% in patients with ischemic heart failure and inflammation. The company is pursuing approval pathways for Revascor across various heart failure conditions, including pediatric congenital heart disease and adults with ischemic HFrEF.
Mesoblast ha annunciato risultati significativi dal loro studio di fase 3 DREAM-HF, pubblicato nell'European Journal of Heart Failure. Lo studio ha dimostrato che un'unica iniezione intramiocardica di Revascor (rexlemestrocel-L) ha migliorato la sopravvivenza in pazienti ad alto rischio con insufficienza cardiaca ischemica e infiammazione. La terapia ha ridotto il rischio di mortalità cardiovascolare dell'80% nei pazienti con infiammazione e ha diminuito gli eventi avversi cardiovascolari maggiori (MACE) dell'88% nei pazienti con insufficienza cardiaca ischemica e infiammazione. L'azienda sta perseguendo percorsi di approvazione per Revascor in varie condizioni di insufficienza cardiaca, inclusa la malattia cardiaca congenita pediatrica e gli adulti con HFrEF ischemica.
Mesoblast anunció resultados significativos de su ensayo de fase 3 DREAM-HF, publicado en el European Journal of Heart Failure. El estudio mostró que una sola inyección intramiocárdica de Revascor (rexlemestrocel-L) mejoró la supervivencia en pacientes de alto riesgo con insuficiencia cardiaca isquémica e inflamación. La terapia redujo el riesgo de muerte cardiovascular en un 80% en pacientes con inflamación y redujo en un 88% los eventos adversos cardiovasculares mayores (MACE) en pacientes con insuficiencia cardiaca isquémica e inflamación. La empresa está persiguiendo vías de aprobación para Revascor en diversas condiciones de insuficiencia cardiaca, incluyendo la enfermedad cardíaca congénita pediátrica y adultos con HFrEF isquémica.
Mesoblast는 유럽 심부전 저널에 발표된 3상 DREAM-HF 시험의 중요한 결과를 발표했습니다. 연구에 따르면 Revascor (rexlemestrocel-L)의 단일 심근내 주사가 허혈성 심부전 및 염증이 있는 고위험 환자의 생존을 개선한 것으로 나타났습니다. 이 요법은 염증이 있는 환자에서 심혈관 사망 위험을 80% 감소시켰으며, 허혈성 심부전 및 염증이 있는 환자에서 주요 심혈관 사건(MACE)을 88% 감소시켰습니다. 이 회사는 소아 선천성 심장병과 허혈성 HFrEF가 있는 성인을 포함한 다양한 심부전 조건에 대한 Revascor의 승인이 진행 중입니다.
Mesoblast a annoncé des résultats significatifs de son essai de phase 3 DREAM-HF, publié dans l'European Journal of Heart Failure. L'étude a montré qu'une seule injection intramyocardique de Revascor (rexlemestrocel-L) a amélioré la survie des patients à haut risque souffrant d'insuffisance cardiaque ischémique et d'inflammation. La thérapie a réduit le risque de mortalité cardiovasculaire de 80 % chez les patients présentant une inflammation et a diminué de 88 % les événements cardiovasculaires indésirables majeurs (MACE) chez les patients souffrant d'insuffisance cardiaque ischémique et d'inflammation. L'entreprise poursuit des voies d'approbation pour Revascor dans diverses conditions d'insuffisance cardiaque, y compris les malformations cardiaques congénitales pédiatriques et les adultes souffrant d'HFrEF ischémique.
Mesoblast hat bedeutende Ergebnisse aus ihrer Phase-3-Studie DREAM-HF bekannt gegeben, die im European Journal of Heart Failure veröffentlicht wurde. Die Studie zeigte, dass eine einzelne intramiokardiale Injektion von Revascor (rexlemestrocel-L) das Überleben bei Hochrisikopatienten mit ischämischer Herzinsuffizienz und Entzündung verbesserte. Die Therapie verringerte das Risiko kardiovaskulärer Todesfälle um 80 % bei Patienten mit Entzündungen und reduzierte die schwerwiegenden unerwünschten kardiovaskulären Ereignisse (MACE) um 88 % bei Patienten mit ischämischer Herzinsuffizienz und Entzündung. Das Unternehmen verfolgt Genehmigungswege für Revascor bei verschiedenen Herzinsuffizienzbedingungen, einschließlich pädiatrischer angeborener Herzkrankheiten und Erwachsenen mit ischämischer HFrEF.
- Revascor reduced cardiovascular death risk by 80% in patients with inflammation
- 88% reduction in 2-point MACE for patients with ischemic HFrEF and inflammation
- 57% reduction in 2-point MACE for patients with ischemic HFrEF
- FDA provided support for accelerated approval pathway in end-stage ischemic HFrEF patients
- None.
Insights
The Phase 3 DREAM-HF trial results represent a significant breakthrough in heart failure treatment. The data shows Revascor reduced cardiovascular death risk by up to 80% in patients with inflammation and decreased major adverse cardiovascular events (MACE) by 88% in ischemic heart failure patients with inflammation.
The trial's robust design and lengthy 30-month follow-up period provide compelling evidence for Revascor's efficacy. The identification of specific biomarkers (hsCRP and IL-6) for patient selection is particularly valuable, as it allows for precise targeting of those most likely to benefit from the therapy. The dual mechanism of action - addressing both inflammation and cardiac repair - differentiates Revascor from existing treatments that primarily target symptoms.
The FDA's supportive feedback regarding an accelerated approval pathway for LVAD patients, combined with these positive trial results, suggests a potentially expedited route to market. This could position Mesoblast as a pioneer in cell therapy for heart failure, addressing a significant unmet medical need.
These clinical results significantly strengthen Mesoblast's market position in the $97 billion heart failure treatment market. The identification of a specific responsive patient population with clear biomarkers enhances the therapy's commercial potential and could streamline the path to market approval.
The potential for accelerated approval in LVAD patients provides a near-term revenue opportunity, while the broader ischemic heart failure indication represents substantial long-term market potential. The therapy's demonstrated efficacy in reducing both mortality and major adverse events could support premium pricing and favorable reimbursement decisions.
The company's STRO3-immunoselected manufacturing process provides scalability advantages and potential IP protection, important for maintaining market position. However, investors should monitor upcoming regulatory interactions and potential capital requirements for commercialization.
Phase 3 trial results published in European Journal of Heart Failure identify key target population for Mesoblast allogeneic cell therapy
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
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.
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.”
The newly published results showed that over a mean follow-up of 30 months in the DREAM-HF trial:
- 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% and38% , 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) and60% (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) by35% (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) and52% (p=0.018) respectively, in patients with ischemic HFrEF and inflammation (n=158) compared to controls.
“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.”
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).
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.
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.
The mortality rate approaches
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
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.
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 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 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 www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
References / Footnotes
- 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. https://doi.org/10.1002/ejhf.3522
- Perin EC. Et al. Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients with Heart Failure. JACC Vol. 81, No. 9, 2023. https://doi.org/10.1016/j.jacc.2022.11.061
- 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
Forward-Looking Statements
This press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about: the initiation, timing, progress and results of Mesoblast’s preclinical and clinical studies, and Mesoblast’s research and development programs; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast’s ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals (including any future decision that the FDA may make on the BLA for remestemcel-L for pediatric patients with SR-aGVHD), manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast’s product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast’s product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast’s ability to enter into and maintain established strategic collaborations; Mesoblast’s ability to establish and maintain intellectual property on its product candidates and Mesoblast’s ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast’s expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast’s financial performance; developments relating to Mesoblast’s competitors and industry; and the pricing and reimbursement of Mesoblast’s product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.
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For more information, please contact:
| Corporate Communications / Investors | Media |
| Paul Hughes | BlueDot Media |
| T: +61 3 9639 6036 | Steve Dabkowski |
| E: investors@mesoblast.com | T: +61 419 880 486 |
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FAQ
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