Data Shared on First-In-Human Trial for Percutaneous Gene Therapy for Heart Failure
May 29, 2009 - Celladon Corp. this week presented phase 1 data from the Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID), a first-in-human phase 1/2 clinical trial, in a scientific symposium at the 12th Annual American Society of Gene Therapy Meeting.
The phase 1 data showed that MYDICAR had an acceptable safety profile in 12 patients, as determined by study investigators and an independent safety committee. In addition, improvements from baseline to six months were observed across a number of key efficacy parameters important in assessing heart failure status. Efficacy was defined as the mean improvement in at least two of five domains without any worsening in the remaining domains, including a functional six-minute walk test, oxygen consumption, quality of life questionnaire, biomarker activity and left ventricular size and function.
The company said it is encouraged by the meaningful improvements in cardiac function and overall condition of patients that demonstrate the return toward normal intracellular calcium cycling and contractility in some of the heart muscle cells of these very sick patients.
The phase 1 open-label, sequential dose escalation, multi-center phase of the trial was designed to investigate safety and biological effects of restoring SERCA2a enzyme activity in heart muscle cells. The enzyme levels are decreased in late stages of heart failure, and extensive research shows loss of SERCA2a levels represents a common pathway resulting in a defect in the ability of the heart to contract properly. Replacing the enzyme may restore function and reverse heart failure.
The phase 2 randomized, double-blind, placebo-controlled, parallel-group, dose ranging portion of the study is designed to evaluate the use of MYDICAR at two or three dose levels compared to placebo in 37 patients. CUPID is currently enrolling patients with advanced heart failure at 17 U.S. medical centers.
Celladon scientists, led by company co-founder Roger J. Hajjar, M.D., director of the Cardiovascular Research Center at Mount Sinai School of Medicine, New York, developed MYDICAR for restoring the SERCA2a calcium transporter in heart failure and validated the overall beneficial effects on cardiac function. MYDICAR is a recombinant adeno-associated viral (rAAV) vector that transfers the SERCA2a gene into heart muscle cells. MYDICAR is delivered in a single dose directly to the heart muscle during a short outpatient procedure, performed in a standard cardiac catheterization laboratory via a small incision in the upper leg.
Of the 12 patients treated, two with low levels of pre-existing antibodies to the AAV vector did not show improvement in these parameters. The data are consistent with safety established for other rAAV vectors, which has been demonstrated in clinical studies of more than 500 patients. AAV vectors are the product of decades of research focused on the safety of gene transfer agents, and are derived from components of a nonreplicating, nonpathogenic, commonly occurring human virus. AAV vectors do not integrate into the chromosome and are considered nonmutagenic. In addition, they have not been associated with the types of inflammatory reactions observed in trials involving adenoviral vectors, which are known to induce acute inflammation of tissues due to activation of the body's immune system, the company said.
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