Date: 2015-05-26
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the European Society of Cardiology - Heart Failure 2015
Company: Juventas Therapeutics (USA - OH) Biocardia (USA - CA)
Product: JVS-100
Action
mechanism: gene therapy. JVS-100 is non-viral DNA plasmid that encodes Stromal–cell Derived Factor 1 (SDF-1). JVS-100 has been shown to protect and repair tissue following organ-injury in a broad range of pre-clinical disease models. Juventas Therapeutics 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 regeneration. Study drug was administered directly to the heart via the BioCardia Helical Infusion Catheter (HIC), which is being developed by BioCardia, Inc., of San Carlos, Calif. The system is a steerable, two-catheter system that enables delivery of biologic therapies to the heart muscle from within the chamber of the heart.
Disease: ischemic heart failure
Therapeutic area: Cardiovascular diseases
Country: USA
Trial
details: STOP-HF is an exploratory Phase II study of 93-patients in a double-blind, randomized, placebo-controlled trial being conducted at 15 centers in the United States to evaluate safety and efficacy of a single treatment of JVS-100, a plasmid stromal cell-derived factor 1 (SDF-1) delivered via injection to the endocardium and myocardium of patients with ischemic heart failure. Patients enrolled in STOP-HF have a prior history of a heart attack and years later developed symptomatic heart failure as defined by an ejection fraction (a measurement of how well your heart is pumping) less than or equal to 40 percent and poor quality of life and exercise tolerance as measured by the Minnesota Living with Heart Failure Questionnaire (MLWHQ) and six minute walk distance (6MWD), respectively. Endpoints of STOP-HF include objective echocardiographic parameters of left ventricular remodeling and biomarkers as well as subjective clinical measures of clinical status in heart failure patients. (NCT01643590)
Latest
news: * On May 26, 2015, Juventas Therapeutics, a clinical-stage biotechnology company focused on developing non-viral gene therapies to treat advanced cardiovascular diseases, presented new 12-month data demonstrating that a single administration of Juventas' non-viral DNA plasmid gene therapy, JVS-100, improves cardiac structure, function, serum biomarkers, and clinical status in patients with severe ischemic heart failure one year after treatment. Final 12-month results from the Phase 2 STOP-HF clinical trial were presented in a late-breaking oral presentation at the European Society of Cardiology - Heart Failure 2015 and is in press at the European Heart Journal. "The results from STOP-HF demonstrate that a single administration of 30 mg of JVS-100 has the potential to improve cardiac function, structure, serum biomarkers and clinical status in a population with advanced chronic heart failure who are symptomatic and present with poor cardiac function," stated Marc Penn, M.D., Ph.D., FACC, Founder and Chief Medical Officer for Juventas and Director of Cardiovascular Research and Cardiovascular Medicine Fellowship at Summa Health in Akron, Ohio. "These findings combined with our deep understanding of SDF-1 biology will guide future clinical trials in which we plan to prospectively study the patient population that demonstrated the most pronounced response to JVS-100. In addition, we will further our understanding of JVS-100 by determining if a second administration of drug may enhance benefits beyond those we observed with a single administration." When delivered directly to a site of tissue injury, JVS-100 induces expression of SDF-1 protein into the local environment for a period of approximately three weeks. The secretion of SDF-1 has been shown to create a homing signal that recruits the body's own stem cells to the site of injury to induce tissue repair and regeneration. Juventas is developing JVS-100 for treatment of advanced chronic cardiovascular disease, including heart failure and late stage peripheral artery disease. "The magnitude and confluence of improvements in key cardiac parameters as observed in STOP-HF have historically translated to reductions in heart failure hospitalizations and mortality in larger studies," added Dr. Penn. "We believe repairing heart tissue in a way that leads to improved function, as we have done with JVS-100, is critical for improving outcomes for these difficult to treat patients who live with the symptoms of chronic heart failure daily." In the full study population patients receiving the 30 mg dose demonstrated improvements at 12 months after treatment in objective measures of cardiac function and structure relative to placebo-treated patients as measured by median change in left ventricle ejection fraction, LVEF (3.5% over placebo) and left ventricular end-systolic volume, or LVESV (8.5 ml over placebo). A composite score comprising change from baseline in six-minute walk distance and the Minnesota Living with Heart Failure Questionnaire also showed a trend toward improved clinical status for 30 mg JVS-100 treated patients (2.5 points); however, the increase in the composite score in patients that receive placebo (2.0 points) led to the trial missing its primary end-point at 4 months. Importantly, as in other trials with JVS-100 there were no unanticipated serious adverse events related to the drug reported for the study. A pre-specified sub-analysis evaluating JVS-100 in patients with the lowest tertile LVEF at the time of enrollment, demonstrated an 11% increase (p<0.01) in LVEF 1 year after patients received 30 mg of JVS-100. In this high risk group of patients, 30 mg of JVS-100 also led to clinically meaningful improvements in LVESV of -34 ml, NTproBNP of -784 pg/ml and stroke volume of 25 ml. These same patients demonstrated a clinically meaningful improvement in composite score of 2.5, compared 1.2 in the placebo treated group. These patients had a baseline LVEF of 26%, placing them in a severe heart failure population with a 40% two year mortality rate. *On May 19, 2014, Juventas Therapeutics presented top-line interim data from a Phase II study evaluating safety and efficacy of JVS-100 in patients with symptomatic ischemic cardiomyopathy at the European Society of Cardiology- Heart Failure Congress in Athens, Greece. In an oral presentation accepted as a late-breaking clinical trial, Marc Penn, M.D., Ph.D., Founder and Chief Medical Officer for Juventas and Director of Cardiovascular Research at Summa Health System, Akron, Ohio, presented the interim data from the STOP-HF trial that shows JVS-100, a non-viral gene therapy expressing stromal cell-derived factor 1 (SDF-1), improves cardiac function in patients with advanced heart failure more than a decade after having a heart attack. SDF-1 has been shown in previous studies to promote tissue repair through activating an endogenous stem cell repair pathway. At the time of the interim analysis, 93 ischemic symptomatic cardiomyopathy patients with prior history of a heart attack were randomized on a 1:1:1 ratio to receive a single treatment of either 15 mg or 30 mg of JVS-100 or matching placebo. Objective and subjective measures of clinical status are being assessed in all patients at 120 days (4 months), and 360 days (12 months) post-injection. The study demonstrated that JVS-100 was well tolerated in all patients with no serious side effects. To date, JVS-100 has been safely delivered to more than 150 patients across multiple clinical trials. Interim top-line four-month efficacy data demonstrated dose-dependent improvements in echocardiographic parameters and biomarkers for patients having received JVS-100. Specifically, a subpopulation of high risk patients who received the high dose of JVS-100 (30 mg) demonstrated improvements relative to placebo in left ventricular end systolic volume (LVESV) p<0.05, left ventricular end diastolic volume (LVEDV) p=0.11, left ventricular ejection fraction (LVEF) p=0.23 and NTproBNP levels (a simple blood test that predicts the risk of worsening heart failure in patients with known cardiovascular disease) p=0.12. “The structural improvements to the heart in STOP-HF patients observed at four months in response to JVS-100 are compelling, especially in patients with more advanced disease, who represent a high risk heart failure population,” said Eugene Chung, M.D., FACC, co-principal investigator for the trial and Director, Advanced Heart Failure Program at The Christ Hospital. “The data suggests that the SDF-1 pathway induces left ventricular remodeling leading to trends of clinically meaningful volume reductions in patients. The literature has shown that improved cardiac function correlates with improved patient outcomes. The clinically meaningful changes we are observing in end systolic volumes and ejection fraction warrant further clinical investigation of JVS-100 as a potential therapy for heart failure.”
