FDA Grants RMAT Designation to Revascor® for Children with Congenital Heart Disease

Earlier this year, the FDA granted Revascor both Rare Pediatric Disease Designation (RPDD) and Orphan-Drug Designation (ODD) for congenital heart disease. Mesoblast Limited, a leading global company in allogeneic cellular medicines for inflammatory diseases, announced that the FDA has granted its second-generation allogeneic stromal cell therapy Revascor (rexlemestrocel-L) Regenerative Medicine Advanced Therapy (RMAT) designation. This decision was based on results from a randomized controlled trial in children with hypoplastic left heart syndrome (HLHS), a severe congenital heart condition.

Mesoblast's Chief Executive, Silviu Itescu, expressed gratitude for the FDA's support in recognizing the potential impact of Revascor on long-term outcomes for critically ill children. With the RMAT designation, Mesoblast plans to discuss a potential approval pathway with the FDA.

The RPDD status indicates that HLHS is a severe or life-threatening disease that primarily affects individuals aged from birth to 18 years. This designation, along with the ODD, acknowledges the rarity of the condition. Upon FDA approval of a Biologics License Application (BLA) for Revascor to treat HLHS, Mesoblast may be eligible for a Priority Review Voucher (PRV). This voucher can be redeemed for any subsequent marketing application or sold to a third party.

RMAT designations are designed to facilitate the development of regenerative medicine therapies aimed at treating, modifying, reversing, or curing serious or life-threatening diseases. Preliminary clinical evidence must show that the therapy has the potential to address unmet medical needs. The RMAT designation for rexlemestrocel-L includes benefits such as rolling review and eligibility for priority review upon BLA filing.

Results from a randomized, placebo-controlled trial of Revascor in children with HLHS were published in the December 2023 issue of The Journal of Thoracic and Cardiovascular Surgery Open. The trial was conducted in the United States and involved 19 children. A single intramyocardial administration of Revascor during staged surgery led to significantly larger increases in left ventricular volumes over 12 months compared to controls, as measured by 3D echocardiography. These changes indicate clinically important growth of the small left ventricle, essential for successful surgical correction to achieve full biventricular (BiV) conversion. Without full BiV conversion, the right heart chamber faces excessive strain, increasing the risk of heart failure, liver failure, and death.

Hypoplastic Left Heart Syndrome (HLHS) is a critical congenital heart disease where the left side of the heart fails to develop properly, reducing the effective pumping of oxygenated blood by the left ventricle to the body. Immediate surgery after birth is crucial, as HLHS is responsible for a significant percentage of neonatal cardiac mortality. Long-term surgical goals involve creating a two-ventricle circulation with the left ventricle pumping blood to the body and the right ventricle to the lungs. However, this is often limited by the insufficient growth of the left ventricle in most patients.

Revascor is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells. It has multiple mechanisms of action beneficial to children with HLHS, including neovascularization, anti-fibrosis, anti-apoptosis, immunomodulation, reduction in inflammation, and reversal of endothelial dysfunction. In a separate trial (DREAM-HF) involving 565 adult patients with heart failure with low ejection fraction (HFrEF), a single intramyocardial administration of Revascor led to significant improvement in left ventricular ejection fraction at 12 months, indicating enhanced overall LV systolic function. The greatest benefit was observed in patients with HFrEF with ischemia and inflammation, who are at the highest risk of mortality.

Mesoblast is a leader in developing allogeneic cellular medicines for severe and life-threatening inflammatory conditions. The company has a broad portfolio of late-stage product candidates based on its mesenchymal lineage cell therapy technology platform. Mesoblast's proprietary manufacturing processes enable the production of industrial-scale, cryopreserved, off-the-shelf cellular medicines, making them readily available to patients worldwide. The company has developed product candidates for various indications, including remestemcel-L for inflammatory diseases and rexlemestrocel-L for advanced chronic heart failure and chronic low back pain. Two of its products have been commercialized in Japan and Europe through licensees, and Mesoblast has established commercial partnerships in Europe and China for certain Phase 3 assets. The company operates in Australia, the United States, and Singapore and is listed on the Australian Securities Exchange (MSB) and Nasdaq (MESO).