Juventas Therapeutics completes enrollment of Phase I/II RETRO-HF trial and demonstrates safety for retrograde infusion of JVS-100 in patients with heart failure
CLEVELAND, Aug. 12, 2014 /PRNewswire-USNewswire/ -- Juventas Therapeutics, Inc., a private clinical-stage company developing a drug-based approach to regenerative medicine today announced that it 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 are already 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 30 mg or 45 mg 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 30 mg or 45 mg 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," states Dr. Amit Patel Director of Cardiovascular Regenerative Medicine at University of Utah and co-Principal
Investigator for the trial. "Throughout the Phase I and II arms of this trial we continued success with the procedure. 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), 6-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," states 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. We are looking forward to seeing the placebo-controlled data from the Phase II RETRO-HF arm to better understand the efficacy of JVS- 100 using retrograde infusion delivery in patients with heart failure."
About Juventas Therapeutics
Juventas Therapeutics, headquartered in Cleveland, Ohio, is a privately held clinical-stage biotechnology company developing a pipeline of regenerative therapies to treat life–threatening diseases. Founded in 2007 with an exclusive license from Cleveland Clinic, Juventas has transitioned its therapeutic platform from concept to through mid-stage clinical trials for treatment of heart failure and critical limb ischemia. Investors include Triathlon Medical Venture Partners, New Science Ventures, Fletcher Spaght Ventures, Tak eda Ventures, Venture Investors, Early Stage Partners, Reservoir Venture Partners, and Cleveland Clinic. The company has also received financial support through the Ohio Third Frontier-funded Global Cardiovascular Innovation Center, Center for Stem Cell & Regenerative Medicine
and the National Center for Regenerative Medicine.
The company's lead product, JVS-100 encodes Stromal–cell Derived Factor 1 (SDF–1). JVS-100 is a non-viral DNA plasmid that has been shown to protect and repair tissue following organ–injury in a broad range of pre–clinical disease models. The first clinical targets will be treatment of patients with symptomatic heart failure and critical limb ischemia. The company has demonstrated in pre-clinical models that JVS-100 therapy has the potential to repair tissue-damage following ischemic injury by recruiting the body's own stem cells to the damaged region, the prevention of cardiac cell death and promotion of new blood vessel growth in the heart. In addition to heart failure, Juventas is also developing JVS-100 for additional indications including acute myocardial infarction, chronic angina, and muscle