FDA Grants Revascor® (Rexlemestrocel-L) Regenerative Medicine Advanced Therapy (RMAT) Designation in Children with Congenital Heart Disease
Mesoblast (MESO) announced that the FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation for Revascor® (rexlemestrocel-L) for treating children with hypoplastic left heart syndrome (HLHS). This follows earlier Rare Pediatric Disease Designation (RPDD) and Orphan-Drug Designation (ODD) granted by the FDA.
Results from a randomized controlled trial with 19 children showed that Revascor administration significantly improved left ventricular volumes over 12 months compared to controls. This growth of the small left ventricle is important for successful surgical correction, enabling normal two-ventricle circulation and reducing risks of heart failure, liver failure, and death.
The RMAT designation provides benefits including Breakthrough and Fast Track designations, rolling review, and priority review eligibility for the Biologics License Application (BLA).
Mesoblast (MESO) ha annunciato che la FDA ha concesso la designazione di Regenerative Medicine Advanced Therapy (RMAT) per Revascor® (rexlemestrocel-L) per il trattamento dei bambini con sindrome del cuore sinistro ipoplastico (HLHS). Questo segue le precedenti designazioni di Rare Pediatric Disease Designation (RPDD) e Orphan-Drug Designation (ODD) concesse dalla FDA.
I risultati di uno studio controllato randomizzato con 19 bambini hanno mostrato che l'amministrazione di Revascor ha migliorato significativamente i volumi ventricolari sinistri nel corso di 12 mesi rispetto ai gruppi di controllo. Questa crescita del piccolo ventricolo sinistro è fondamentale per una corretta correzione chirurgica, consentendo una normale circolazione a due ventricoli e riducendo i rischi di insufficienza cardiaca, insufficienza epatica e morte.
La designazione RMAT offre vantaggi come le designazioni Breakthrough e Fast Track, revisione continua e idoneità per una revisione prioritaria della Domanda di Licenza Biologica (BLA).
Mesoblast (MESO) anunció que la FDA ha otorgado la designación de Regenerative Medicine Advanced Therapy (RMAT) para Revascor® (rexlemestrocel-L) para el tratamiento de niños con síndrome del corazón izquierdo hipoplásico (HLHS). Esto sigue a las designaciones anteriores de Rare Pediatric Disease Designation (RPDD) y Orphan-Drug Designation (ODD) otorgadas por la FDA.
Los resultados de un ensayo controlado aleatorio con 19 niños mostraron que la administración de Revascor mejoró significativamente los volúmenes del ventrículo izquierdo durante 12 meses en comparación con los controles. Este crecimiento del pequeño ventrículo izquierdo es importante para una corrección quirúrgica exitosa, permitiendo una circulación normal de dos ventrículos y reduciendo los riesgos de insuficiencia cardíaca, insuficiencia hepática y muerte.
La designación RMAT proporciona beneficios como las designaciones Breakthrough y Fast Track, revisión continua y elegibilidad para revisión prioritaria en la Solicitud de Licencia Biológica (BLA).
Mesoblast (MESO)는 FDA가 재생 의학 진보 치료 (RMAT) 지정을 Revascor® (rexlemestrocel-L)에게 심첨 심장 증후군 (HLHS)을 앓고 있는 아동 치료에 대해 부여했다고 발표했습니다. 이는 FDA에 의해 이전에 부여된 희귀 소아 질환 지명 (RPDD)과 오르판 약물 지명 (ODD)에 이어진 것입니다.
19명의 아동을 대상으로 한 무작위 대조 시험 결과, Revascor 투여가 12개월 동안 대조군에 비해 좌심실 용적을 유의미하게 증가시켰습니다. 좌심실의 성장은 성공적인 수술 교정을 위해 중요하며, 정상적인 이심실 순환을 가능하게 하고 심부전, 간부전 및 사망의 위험을 줄입니다.
RMAT 지정은 돌파구 및 패스트 트랙 지명, 연속 검토, 생물학적 라이센스 신청서 (BLA)에 대한 우선 검토 자격을 포함하는 혜택을 제공합니다.
Mesoblast (MESO) a annoncé que la FDA a accordé la désignation de Thérapie Avancée en Médecine Régénérative (RMAT) pour Revascor® (rexlemestrocel-L) pour le traitement des enfants atteints de syndrome du cœur gauche hypoplasique (HLHS). Cela fait suite aux précédentes désignations de Maladie Pédiatrique Rare (RPDD) et de Médicament Orphelin (ODD) accordées par la FDA.
Les résultats d'un essai contrôlé randomisé portant sur 19 enfants ont montré que l'administration de Revascor a amélioré de manière significative les volumes ventriculaires gauches sur 12 mois par rapport aux témoins. Cette croissance du petit ventricule gauche est importante pour une correction chirurgicale réussie, permettant une circulation normale à deux ventricules et réduisant les risques d'insuffisance cardiaque, d'insuffisance hépatique et de décès.
La désignation RMAT offre des avantages tels que les désignations Breakthrough et Fast Track, l'examen continu et l'éligibilité à un examen prioritaire pour la Demande de Licence Biologique (BLA).
Mesoblast (MESO) gab bekannt, dass die FDA die Regenerative Medicine Advanced Therapy (RMAT) -Einstufung für Revascor® (rexlemestrocel-L) zur Behandlung von Kindern mit hypoplastischem Linksherzsyndrom (HLHS) genehmigt hat. Dies folgt den vorherigen Einstufungen als Rare Pediatric Disease Designation (RPDD) und Orphan-Drug Designation (ODD), die von der FDA gewährt wurden.
Die Ergebnisse einer randomisierten kontrollierten Studie mit 19 Kindern zeigten, dass die Verabreichung von Revascor die Volumina des linken Ventrikels signifikant über 12 Monate hinweg im Vergleich zu den Kontrollen verbesserte. Dieses Wachstum des kleinen linken Ventrikels ist wichtig für eine erfolgreiche chirurgische Korrektur, da es eine normale Zweiventrikelschaltung ermöglicht und das Risiko von Herzinsuffizienz, Leberinsuffizienz und Tod verringert.
Die RMAT-Einstufung bietet Vorteile wie die Einstufungen Breakthrough und Fast Track, kontinuierliche Überprüfung und die Berechtigung zur Prioritätsprüfung für den Antrag auf biologisches Zulassungsverfahren (BLA).
- RMAT designation received, expediting development and review process
- Successful clinical trial results showing significant improvement in left ventricular volumes
- Potential eligibility for Priority Review Voucher upon BLA approval
- Multiple FDA designations (RMAT, RPDD, ODD) strengthening market position
- Small trial size of only 19 children may require additional studies
- Full FDA approval still pending and not guaranteed
Insights
The FDA's RMAT designation for REVASCOR represents a significant regulatory milestone that could accelerate the therapy's path to market. The designation, combined with previously granted Rare Pediatric Disease and Orphan Drug designations, provides multiple regulatory advantages including priority review and potential eligibility for a valuable Priority Review Voucher upon approval.
The clinical trial results are particularly promising, showing statistically significant improvements in left ventricular volumes (p=0.009 & p=0.020). This is important for HLHS patients, as increased left ventricle size could enable full biventricular conversion, potentially reducing mortality risks and improving long-term outcomes.
For Mesoblast, this triple designation status strengthens their market position in regenerative medicine and could substantially expedite the approval process. The potential PRV alone represents significant value, as these vouchers have historically sold for
This regulatory development significantly enhances Mesoblast's commercial prospects in the pediatric cardiac market. With a market cap of
The potential Priority Review Voucher represents a valuable asset, either for the company's future programs or as a tradeable commodity. Recent PRV transactions have ranged from
The therapy's unique position in treating HLHS, a serious unmet medical need, could support premium pricing and rapid market adoption if approved. This could translate into meaningful revenue potential given the therapy's apparent efficacy and the lack of effective alternatives.
Earlier this year FDA granted REVASCOR both Rare Pediatric Disease Designation (RPDD) and Orphan-Drug Designation (ODD) for congenital heart disease
NEW YORK, Dec. 04, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced the United States Food and Drug Administration (FDA) has granted its second generation allogeneic, STRO3-immunoselected, and industrially manufactured stromal cell therapy Revascor® (rexlemestrocel-L) Regenerative Medicine Advanced Therapy (RMAT) designation following submission of results from the randomized controlled trial in children with hypoplastic left heart syndrome (HLHS), a potentially life threatening congenital heart condition.
Mesoblast Chief Executive Silviu Itescu said: “We appreciate FDA’s support in designating REVASCOR both RMAT and RPD status, a recognition of the potential impact of our therapy on the long-term adverse outcomes of these desperately ill children. Under the RMAT designation, we plan to meet with FDA to discuss a potential approval pathway in this indication.”
Earlier this year, FDA granted REVASCOR both Rare Pediatric Disease Designation (RPDD) and Orphan-Drug Designation (ODD) for treatment of children with HLHS. RPDD demonstrates that the disease is serious or life-threatening and the manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents, and that the disease is a rare disease or condition. On FDA approval of a BLA for REVASCOR for the treatment of HLHS, Mesoblast may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed for any subsequent marketing application or may be sold or transferred to a third party.
RMAT designations aim to expedite the development of regenerative medicine therapies intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition where preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for the disease or condition. An RMAT designation for rexlemestrocel-L provides all the benefits of Breakthrough and Fast Track designations, including rolling review and eligibility for priority review on filing of a Biologics License Application (BLA).
Results from a blinded, randomized, placebo-controlled prospective trial of REVASCOR conducted in the United States in children with HLHS were published in the December 2023 issue of the peer reviewed The Journal of Thoracic and Cardiovascular Surgery Open (JTCVS Open).1 In the HLHS trial conducted in 19 children, a single intramyocardial administration of REVASCOR at the time of staged surgery resulted in the desired outcome of significantly larger increases in left ventricular (LV) end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography, (p=0.009 & p=0.020 respectively).
These changes are indicative of clinically important growth of the small left ventricle, facilitating the ability to have a successful surgical correction, known as full biventricular (BiV) conversion, which allows for a normal two ventricle circulation with the surgically repaired left ventricle taking over circulatory support to the body. Without full BiV conversion the right heart chamber is under excessive strain with increased risk of heart failure, liver failure, and death.
About Hypoplastic Left Heart Syndrome (HLHS)
HLHS is a severe congenital heart disease in which the left side of the heart does not fully develop and effective pumping of oxygenated blood by the left ventricle to the rest of the body is reduced. Without immediate surgery after birth, the prognosis is dismal with HLHS overall being responsible for
About Revascor® (rexlemestrocel-L) in Heart Disease
REVASCOR is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells which have been shown previously to have multiple mechanisms-of-action that may be beneficial to children with HLHS including neovascularization, anti-fibrosis, anti-apoptosis, immunomodulation, reduction in inflammation, and reversal of endothelial dysfunction. In the DREAM-HF randomized sham-placebo controlled prospective trial of REVASCOR in 565 randomized adult patients with heart failure with low ejection fraction (HFrEF), a single intramyocardial administration of REVASCOR into the left ventricle resulted in significant improvement in LV ejection fraction at 12 months,3 indicative of strengthened overall LV systolic function. The greatest treatment benefit was on 2- and 3-Point Major Adverse Cardiovascular Events (MACE), particularly in patients with HFrEF with ischemia and inflammation, who are at highest risk of mortality.4
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
- Wittenberg RE, Gauvreau K, Leighton J, Moleon-Shea M, Borow KM, Marx GR, Emani SM, Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome, JTCVS Open Volume 16, Dec 2023, doi: https://doi.org/10.1016/j.xjon.2023.09.031
- Kritzmire, S. M, et al. (2022). Hypoplastic left heart syndrome.
- 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
- 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
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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FAQ
What is the latest FDA designation received by Mesoblast (MESO) for Revascor?
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