Sunjay Kaushal,Eric Naioti,Kevin Ramdas,Danial Mehranfard,Lisa McClain‐Moss,Michael Davis,Linda M. Lambert,Shaji C. Menon,Narutoshi Hibino,David L.S. Morales,Adil Husain,Kaitlyn Masih,Kristopher B. Deatrick,Sarah Speed,Anthony A. Oliva,Joshua M. Hare
Hypoplastic left heart syndrome (HLHS) is a univentricular congenital heart defect that has high morbidity and mortality and requires three-stage surgical reconstruction so that the right ventricle (RV) delivers systemic circulation. Poor outcomes result from RV failure in the systemic position. Accordingly, we conducted a phase I clinical trial (called ELPIS) of Lomecel-B™, an allogeneic bone-marrow derived cell-based therapy designed to improve cardiovascular performance, delivered as a one-time treatment during the Stage II (Glenn) surgery at approximately 4 months after birth. This trial met its primary endpoint (safety through 1-year post-treatment). To assess whether Lomecel-B™ has survival benefits, all ELPIS patients ( n=10, 7 males, and 3 females) were enrolled in a multi-year follow-on study and compared to a retrospective control group which was identified by a relevant clinical HLHS database. Patients in both studies were assessed for up to 5 years (range 3.5 - 5.0 years post-treatment for ELPIS) for mortality, heart transplants, and stage III (Fontan) surgery. Outcomes were compared with long-term historical data from patients in the Single Ventricle Reconstruction (SVR) Trial receiving the same shunt type at Stage I (Norwood) operation. 5-year Kaplan-Meier survival was 100% in ELPIS patients with none requiring heart transplant. This compared to 81.6% (95% CI= [76.5, 87.0]) transplant-free survival in the SVR trial through 5 years post-Glenn surgery, and a 5.2% (95% CI= [2.0, 8.3]) heart transplantation rate (Figure 1). No stem cell related safety issues were reported. These findings support Lomecel-B™ as a potential adjunct to HLHS reconstruction surgery to improve clinical benefits and reduce the need for subsequent heart transplantation. Further long-term follow-up and controlled trials are both warranted and underway.