Juventas Therapeutics, a private, clinical-stage company developing a drug-based approach to regenerative medicine, has successfully completed the phase I arm of the RETRO-HF clinical trial, and fully enrolled the phase II arm that is evaluating the safety and preliminary clinical efficacy for retrograde infusion of JVS-100 in patients with heart failure.

JVS-100 is a non-viral plasmid that encodes for stromal cell-derived factor-1 (SDF-1). SDF-1 promotes cardiac function and tissue repair in patients who have had a heart attack and have heart failure years later through activation of the body's natural stem cell based regenerative repair processes.

Juventas recently reported interim results from its phase II STOP-HF trial, which demonstrated that JVS-100 delivered via endo-ventricular injection using the BioCardia Helical Infusion Catheter is safe and demonstrated clinically meaningful improvements in objective measures of cardiac function and biomarker parameters in patients with advanced heart failure.

Retrograde infusion is a minimally invasive technique in which a catheter is inserted through the venous system into a patient's coronary sinus. A balloon is then inflated in order to temporarily block blood flow in the vein of the heart so that the gene therapy can be infused directly into the heart. The technique employs commonly used balloons and catheters that already are approved for delivery of therapeutic agents to the heart.

The phase I RETRO-HF trial is a 12-person open-label, dose-escalation study to evaluate the safety of performing retrograde infusion of JVS-100 dosed at 30mg or 45mg to patients with ischemic symptomatic heart failure. The procedure was safely performed in all 12 patients with 11 receiving the full JVS-100 dose. There were no unanticipated procedural or drug related adverse events.

Upon meeting a one-week safety endpoint, an independent Data Safety Monitoring Committee (DSMC) allowed commencement of the phase II RETRO-HF arm, a 60-patient randomized, double-blinded, placebo-controlled arm in which patients will receive JVS-100 at 30mg or 45mg or a placebo infusion.

"The phase I RETRO-HF trial is the first FDA-allowed study to demonstrate that retrograde infusion can be used to safely deliver gene therapy to the heart," said Dr. Amit Patel, director of cardiovascular regenerative medicine at University of Utah and co-Principal Investigator for the trial. "Gene therapies are a growing focus in the heart failure field and clinical validation of multiple delivery systems to allow for effective cardiac delivery will be important as they advance through clinical development toward commercialization."

In addition to meeting its safety endpoint, the phase I RETRO-HF study demonstrated preliminary signs of clinical efficacy across several key parameters at four months post treatment. Clinically meaningful trends in improvement were observed over baseline in left ventricular end systolic volumes, left ventricular end diastolic volumes, left ventricular ejection fraction (LVEF), six-minute walk distance (6MWD) and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ).

"The cardiac benefits observed in the open-label phase I RETRO-HF support earlier studies evaluating the role of JVS-100 in patients with advanced ischemic heart failure," said Eugene Chung, M.D., FACC, co-principal investigator for STOP-HF and RETRO-HF and director of heart failure at the Ohio Heart and Vascular Center. "We are observing structural stabilization or improvement in the size of the heart in the majority of treated patients. Multiple studies have shown that reduced cardiac volumes correlate highly with better clinical outcomes.”