Cell Therapy Gets RMAT Designation for HLHS, Improves Survival in Heart Failure With Reduced Ejection Fraction

Emerson C. Perin, MD, PhD

Credit: The Texas Heart Institute

The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Mesoblast’s rexlemestrocel-L (Revascor) stromal cell therapy for the potential treatment of children with hypoplastic left heart syndrome (HLHS).¹

Rexlemestrocel-L is an allogeneic mesenchymal precursor cell therapy. The RMAT designation follows previous Rare Pediatric Disease and Orphan-Drug Designations for rexlemestrocel-L in this indication.

“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,” Silviu Itescu, MD, chief executive officer, Mesoblast, said in a statement.¹

Mesoblast previously reported data on rexlemestrocel-L in a phase 1/2 randomized, controlled trial (NCT03079401) at Boston Children's Hospital in 19 children with HLHS. These participants received a single intramyocardial administration of REVASCOR at the time of staged surgery which resulted in significantly larger increases in left ventricular (LV) end-systolic (P = .009) and end-diastolic volumes (P = .020) over 12 months compared with controls as measured by 3D echocardiography.²

Rexlemestrocel-L also just recently demonstrated improved survival in treated patients with progressive heart failure with reduced ejection fraction (HFrEF) and inflammation in data from the phase 3 DREAM-HF trial published in European Journal of Heart Failure.³

“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,” lead investigator, Emerson C. Perin, MD, PhD, Medical Director, The Texas Heart Institute, said in an earlier statement.⁴

Perin and colleagues found that over a 30-month mean follow-up, a single intramyocardial rexlemestrocel-L administration reduced 2-point major adverse cardiovascular events (MACE; myocardial ischemia [MI] or stroke) by 88% (P = .005) and 3-point MACE (MI, stroke, or cardiovascular death [CVD])by 52% (P = .018) in patients with ischemic HFrEF and inflammation compared to controls.³

The investigators also found that in the control group, the greatest risk factors for CVD were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; P = .003), which yielded a 61% increased risk,and ischemicHFrEFaetiology (P = .097), which yileded a 38% increased risk.³

“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,” Itescu said.⁴ “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.”

REFERENCES

1. FDA Grants Revascor® (Rexlemestrocel-L) Regenerative Medicine Advanced Therapy (RMAT) Designation in Children with Congenital Heart Disease. News release. Mesoblast. December 4, 2024. https://www.globenewswire.com/news-release/2024/12/04/2991984/0/en/FDA-Grants-Revascor-Rexlemestrocel-L-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-in-Children-with-Congenital-Heart-Disease.html

2. Wittenberg RE, Gauvreau K, Leighton J, et al. Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome. JTCVS Open. 2023 (16): 656-672. doi: 10.1016/j.xjon.2023.09.031

3. Perin EC, Borow KM, Henry TD, et al. Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF. Eur J Heart Fail. Published online November 26, 2024. doi:10.1002/ejhf.3522

4. Revascor Improves Survival and Reduces Major Morbidity in High-Risk Ischemic Heart Failure Patients With Inflammation. News release. Mesoblast. December 2, 2024. https://www.globenewswire.com/news-release/2024/12/02/2990209/0/en/Revascor-Improves-Survival-and-Reduces-Major-Morbidity-in-High-Risk-Ischemic-Heart-Failure-Patients-With-Inflammation.html