December 12, 2013 — BioCardia Inc., a cardiovascular regenerative medicine company, announced positive 12-month results for the randomized Transendocardial Autologous Cells (MSC or BMC) in Ischemic Heart Failure Trial (TAC-HFT). The Phase II trial demonstrated the safety of transendocardial stem cell injection (TESI) of autologous culture-expanded mesenchymal cells (MSCs) and autologous minimally processed whole bone marrow mononuclear cells (BMCs) delivered by the company’s Helical Infusion Catheter System in the treatment of chronic ischemic cardiomyopathy (ICM). The trial results were concurrently reported in the Journal of the American Medical Association (JAMA) and presented by Joshua Hare, M.D., University of Miami, and lead investigator, as a late-breaking presentation at the American Heart Association’s 2013 Scientific Sessions.
In the JAMA paper, the authors concluded, “In this preliminary study, TESI with autologous MSCs or BMCs appeared to be safe in patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.”
“Safety and efficacy outcomes for both combination therapies were encouraging in this Phase II trial,” said Hare. “We believe a high dosage of 200 million cells delivered in a stable and precise way with the Helical Infusion Catheter System is contributing to these positive results.”
The TAC-HFT Trial is a Phase I/II randomized, double-blind, placebo-controlled study of 65 patients with chronic ischemic left ventricular (LV) dysfunction due to ischemic cardiomyopathy (ICM), co-sponsored by the University of Miami and BioCardia. Patients were randomized to receive a dose of 200 million stem cells of either MSCs or BMCs delivered to 10 LV sites in the myocardium via TESI using the Helical Infusion Catheter System. This precise approach to infusion combines an ultra-flexible distal catheter, a helix-shaped needle to fixate to the myocardial tissue and contrast delivered from the needle base to confirm engagement with the tissue.
Both therapies met the primary endpoint of the trial by demonstrating no incidence of treatment-emergent serious adverse events (TE-SAEs) at 30 days. TE-SAEs were defined as the composite of death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade or sustained ventricular arrhythmias (>15 seconds or causing hemodynamic compromise). No significant post-procedural pericardial effusion was evident, and the technical success of transendocardial infusion with the Helical Infusion Catheter was 100 percent.
At 12 months, the BMC therapy group had no incidence of major adverse cardiac events (MACE), while one MACE occurred in the MSC therapy group and the placebo group experienced two incidents of MACE. The rehospitalization rate across groups was similar. No incidence of ectopic tissue formation was evident with either therapy. Two deaths occurred during the trial, one each in the MSC therapy group and placebo group.
The JAMA paper also cites 12-month outcomes for this Phase II trial designed for safety that showed functional and quality of life improvements for both the MSC and BMC therapies in pre-specified secondary endpoints. Compared to baseline measures, Minnesota Living with Heart Failure (MLHF) scores were statistically significant for both therapies. Only MSC patients showed statistically significant improvement when assessed with a repeated measures statistical analysis for the 6-Minute Walk Test and regional myocardial function. There was no statistical difference between either therapy when compared to placebo in NYHA class, LV chamber volume or LVEF.
“In our second head-to-head trial of two fundamentally different bone marrow cell therapies, both the minimally processed and culture-expanded therapies showed clinical benefit to patients in positive, placebo-controlled data sets,” said Peter Altman, CEO, BioCardia. “With these results, we look forward to approval of a pivotal trial where we, working in partnership with the University of Miami and others, will join the ranks of the three already-approved pivotal trials studying the promising potential of intramyocardial delivery of bone marrow-derived cell formulations in the treatment of cardiovascular disease.”
University of Miami Miller School of Medicine interventional cardiologist co-authors who performed procedures in the trial included Alan Heldman, M.D., and Juan Pablo Zambrano, M.D. Darcy DiFede, RN, coordinated these efforts.
For more information: www.biocardia.com, jama.jamanetwork.com, my.americanheart.org