Clinical program supports accelerated approval filing with CFDA in China, and a Phase 3 program in the U.S.
SAN DIEGO and SHANGHAI, May 23, 2013 /PRNewswire/ -- Zensun Sci & Tech, Ltd., a biopharmaceutical company based in Shanghai and San Diego, announced today positive results of four completed Phase 2 clinical trials including three double-blind, placebo-controlled studies conducted in China and Australia and interim results from the United States Phase 2 trial for Zensun's innovative "first-in-class" anti-heart failure drug, Neucardin™.
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The data demonstrates that Neucardin™ reduced all-cause mortality, improved heart function, reduced heart volumes, improved exercise capacity and quality of life on top of current standard of care in patients with chronic heart failure (CHF). Based on these clinical trial data, Zensun has filed a New Drug Application (NDA) in China to obtain accelerated market approval, and is planning a Phase 3 clinical program in the United States.
"Current treatments for chronic heart failure have improved mortality; however, they have reached their potential and novel therapeutic approaches are required if outcomes in these patients are to improve," said Dr. Inder Anand, a Steering Committee Member for the United States clinical trial, Professor of Medicine at the University of Minnesota and Director of the Heart Failure Program at the Minneapolis VA Medical Center. "Neucardin™ has truly novel mechanisms of action on the failing heart. It targets diseased heart tissue directly via two alternate pathways; one that promotes heart muscle's structural integrity and the other improves the pumping efficiency of the heart."
Global Phase 2 Clinical Trial Results for Neucardin™
Six-hundred and seventy-eight people with CHF have participated in the Neucardin™ clinical studies. Overall, the Phase 2 clinical studies demonstrated a 3 to 5% placebo corrected improvement in left ventricular ejection fraction, (LVEF) (p<0.05).
The results of three completed Phase 2 clinical studies from both China and Australia show that a 10 day intravenous infusion of Neucardin™ for 10 hours a day to New York Heart Association (NYHA) class II-III patients with heart failure increased cardiac function, reversed ventricular remodeling (reduced both left ventricular end systolic and end diastolic volumes), and reduced circulating NT-proBNP levels for up to three months after administration (all independent long-term predictors of mortality and morbidity).
A Phase 2 survival trial in China showed that 23 weekly intravenous bolus injections of NeucardinTM immediately following 10 daily intravenous infusions decreased all-cause mortality of CHF patients at one year by 39% compared with placebo. The survival benefit was even greater (60%) in patients with NYHA class III heart failure or with baseline NT-proBNP levels less than 4000 fmol/ml compared with placebo.
The Phase 2 clinical trial in the United States is a randomized, parallel, placebo-controlled double-blind study conducted at 11 clinical trial sites (active not recruiting).
Sixty-seven patients with NYHA class II and III heart failure, on stable standard of care heart failure medication including implantable defibrillators (ICDs) in all patients, participated in the trial and were centrally randomized to placebo or two doses of Neucardin™. Study drug was administered subcutaneously using a mini pump for 8 hours a day for 10 days. The primary endpoint of the study was change from baseline in LVEF at day 30 after initiation of treatment compared with placebo.
Results of the interim analysis show that at 30 days, both doses of Neucardin™ improved LVEF and reduced LV volumes compared with placebo as determined by both cardiac CT and 2D-echocardiography, and the improvement was maintained for up to 3 months after treatment. Secondary endpoints including exercise tolerance (six-minute walk distance) and quality of life scores (Kansas City Cardiomyopathy Questionnaire) also improved.
The study also demonstrated that Neucardin™ has acceptable safety and pharmacokinetic profiles. Neucardin™ was well-tolerated with most of the adverse events limited to the gastrointestinal disorders such as vomiting, nausea and loss of appetite that recovered when drug administration was stopped, consistent with the safety profiles observed in previous China and Australia trials with intravenous administration of Neucardin™. An integrated safety database available on 747 patients with CHF shows a significantly reduced serious adverse event rate of 5.4% in the Neucardin™ group compared with 11.2% in the placebo group.
"With the increasing global prevalence and cost of CHF management, Zensun has the opportunity to provide this novel treatment for CHF to the world, potentially reducing both morbidity and mortality," said Dr. Mingdong Zhou, CEO and President of Zensun. "The clinical trial results support moving this program forward aggressively in both China and the United States."
Professor Anand further commented on the data, "The short trials including the one that was done in the United States, showed that the pumping function of the heart improved by about three to four percent points. And now if you look at something like a three to four percent improvement in the heart function, it could translate into a 30 to 40 percent reduction in overall mortality. And that is enormous considering that we are giving this drug on top of all the previous drugs that have already shown to have benefit in these patients."
Neucardin™ is a unique peptide that directly targets the diseased cardiac muscle cell known as cardiomyocyte to improve heart function and reduce heart volume. Neucardin™ has completed 8 clinical trials with more than 700 patients with chronic heart failure.
Neucardin™ is a fragment peptide of human Neuregulin 1 that binds to the epidermal growth factor ErbB4 receptor tyrosine kinase (RTK) on cardiac myocytes. Once bound to the ErbB4 RTK receptor on cardiac myocytes, Neucardin™ modulates downstream signaling pathways leading to altered protein expression and regulation. The unique mechanism of action of Neucardin™ is to increase heart function via two key pathways: First, it promotes muscle structural organization by increasing the expression of a novel cardiac-specific myosin light chain (MLC-2v). Activation of cMLCK and MLC-2v are known to increase sarcomere reorganization and cardiac contractility and prevent cardiac decompensation from heart failure. CHF is associated with a pathological transition from the compensated heart to the decompensated heart. Second, Neucardin™ improves heart contraction and relaxation by regulating calcium cycling through the expression of sarcoplasmic reticulum (SR) Ca (2+) ATPase and the ryanodine receptor.
About Chronic Heart Failure
Chronic heart failure is a major burden with an estimated prevalence of approximately 2% of people in the United States alone and an incidence of ~550,000 new cases per year. Despite the spectacular success of β-blockers, angiotensin converting enzyme (ACE) inhibitors, aldosterone receptor blockers and more recently ICD and CRT devices in reducing heart failure morbidity and mortality, the overall prognosis of these patients remains poor with a five-year mortality rate as high as 50% and increasing in the aging population.
Heart failure remains the leading cause of hospital admission among subjects over the age of 65 years and accounts for 1.1 million annual hospitalizations and annual hospital charges of $29 billion U.S. With no novel therapies in the last two decades, there are urgent unmet medical needs for the development of novel therapeutic approaches.
Zensun (Shanghai) Science & Technology Co., Ltd. (www.zensun.com) is an international biopharmaceutical company focused on the development of innovative "first-in-class" biotherapeutic products for the treatment of serious and life-threatening unmet medical needs. It is focused on discovering new medicines using novel disease-specific targets and innovative technologies. Zensun's patented discoveries are then developed into therapies. With adherence to the tenet of "healing for life," Zensun hopes to transform the lives of heart failure and cancer patients by providing them with drugs that treat their disease, not just their symptoms.
To meet the world's highest standards, incorporate international intelligence, and expand the coverage of patients, Zensun has infrastructure established in China, Australia, and the United States. As a globalized biopharmaceutical company, Zensun has gathered experts and pioneers from throughout the world aiming at global commercialization of the novel therapies, and has attracted investors with a forward vision and broad outlook. Zensun leverages the leading technology to best serve its patients and deliver maximum return for investors. Zensun is a paradigm-shifting company which has led the way in novel heart failure and cancer therapies.
SOURCE Zensun USA Inc.