Promising results from a phase 2 study of AC6 gene transfer for the treatment of patients with heart failure and reduced ejection fraction have been published in JAMA Cardiology. The findings indicate that, through one-time administration, AC6 gene transfer safely increased heart function beyond optimal heart failure therapy.
AC6 gene transfer involves infusing an inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6) into the arteries that feed the heart during cardiac catheterization, a commonly performed procedure. Renova Therapeutics is developing AC6 gene transfer as an investigational product known as RT-100.
AC6 is a protein found in cardiac muscle cells that regulates heart function and appears to be down-regulated in heart failure patients. Dr. H. Kirk Hammond, a professor of medicine at the University of California–San Diego, and his colleagues developed the method of gene transfer designed to up-regulate AC6 content in the heart, performed preclinical studies, and conducted the clinical trial. Hammond is a co-founder of Renova Therapeutics.
In the randomized, double-blind, placebo-controlled study, 56 patients were studied for up to one year at seven medical centers in the United States. The trial assessed the safety of five doses of Ad5.hAC6 compared with placebo in patients with symptomatic heart failure. Forty-two patients received Ad5.hAC6, and 14 received placebo.
Compared with placebo, AC6 gene transfer significantly (P = 0.029) increased left ventricular peak, a direct measure of the heart’s ability to fill. AC6 gene transfer also significantly (P = 0.024) increased the left ventricular ejection fraction in patients with non-ischemic heart failure. Symptoms of heart failure were reduced 12 weeks after therapy in Ad5.hAC6-treated subjects but not in subjects given placebo (P = 0.0005).
There were no differences in the rates of serious adverse events between the AC6 and placebo groups. After one year of follow-up, one patient (2.4%) in the AC6-treated group and one patient (7.1%) in the placebo group had died (P = 0.40). The annual heart failure hospital admission rates were 9.5% in the AC6 group compared with 28.6% in the placebo group (P = 0.10).
The study results were published in the April 2016 print issue of JAMA Cardiology.
Source: Renova Therapeutics; March 30, 2016.