Repairon, a biotechnology company developing regenerative cardiac therapies, has announced that clinical results evaluating its engineered human heart muscle tissue for patients with advanced heart failure have been published in the New England Journal of Medicine (NEJM).
The publication concludes that restoration of heart muscle function in patients with advanced heart failure is achievable, resulting in improved health and quality of life.
The data were generated in the BioVAT-HF clinical trial. Designed to assess safety and preliminary efficacy, the phase 1-2 study involved implanting fully functional heart muscle patches engineered from human induced pluripotent stem cell-derived terminally differentiated heart muscle cells onto the weakened left ventricular muscle of patients with advanced heart failure with reduced ejection fraction (HFrEF), alongside guideline-directed medical therapy.
The trial began with a dose-escalation phase to establish the safe maximum dose, followed by treatment at that dose to further evaluate safety and efficacy. Of the 20 patients enrolled, 16 received the safe maximum dose. At the time of reporting, the last enrolled patient had completed 3 months of follow-up, and follow-up across these patients ranged from 6 to 52 months.
Key safety findings indicate that three patients died during the trial from causes that the Data Safety Monitoring Board graded as unrelated to the BioVAT. Severe adverse events were mostly related to underlying heart and concurrent diseases as well as to immunosuppression requiring adaptation of the immunosuppression regimen. Three patients experienced episodes of ventricular tachycardia which were found to be unrelated to the BioVAT transplant. No patients had ventricular fibrillation. Among the 16 safe maximal dose patients, there were heart failure hospitalizations for two patients.
The efficacy findings from the NEJM Publication indicate that for those patients who received the safe maximal dose, from baseline, target heart wall thickness increased 4.5 mm at 3 months and 2.9 mm at 12 months follow-up; left ventricular ejection fraction increased 3.9% at 3 months and 6.9% at the latest timepoint; and quality of Life as measured by KCCQ-OSS increased 6.7 points at 3 months and 15 points at 12 months follow-up.
The study outcomes support preclinical findings that engineered heart muscle can integrate with damaged myocardium, form a vascularised layer, and contract in synchrony with native tissue. This was further confirmed by analysis of an explanted heart from a patient in the dose-finding cohort who later underwent cardiac transplantation, providing clear evidence of human heart remuscularisation and associated increases in wall thickness, ejection fraction, and quality of life. The authors concluded that further clinical investigations with longer follow-up times are warranted.
Wolfram-Hubertus Zimmermann, professor and director of the Institute of Pharmacology and Toxicology at the University Medical Center Goettingen, Germany, and principal author of the NEJM Publication, said: “Heart failure therapies available today can often slow the progression of the disease, but they cannot replace destroyed heart muscle. Our goal, therefore, is to generate new, functional heart muscle tissue and thereby provide targeted support to the weakened heart.”
Lothar Germeroth, Repairon’s CEO, said: “We are highly encouraged by these phase II results, which we believe validate the therapeutic potential of our regenerative cardiac patch platform. Heart failure remains one of the leading causes of morbidity and mortality worldwide, and we believe these findings may open a new chapter in myocardial regeneration and restorative cardiovascular medicine.”
Approximately 5% of the global population suffers from chronic heart failure of any severity, and it remains one of the most common causes of death. In the US, heart failure represents the most common cause of hospitalisation and mortality in the senior population, and over 6m people are affected. As heart failure progresses to advanced stages, patients experience weakness with discomfort during all physical activities and at rest, sometimes even requiring constant bed rest. For these severely ill patients, the only treatment options currently available are mechanical pump devices or heart transplantation.