In a latest Phase II clinical trial conducted at the Mount Sinai School of Medicine, researchers found that cardiac function in people afflicted with severe heart failure could be significantly improved or stabilized by a new gene therapy.

A significant reduction in cardiovascular hospitalizations were observed in patients receiving high dose of SERCA2a therapy. These patients clinically benefited from this therapy, which has long been an unmet need in this population.

The reputed journal, Circulation, by American Heart Association published this data in their issue dated June 27. An adeno-associated virus vector, which is primarily an inactive virus acting as a medication transporter used for the delivery of SERCA2a into cardiac cells.

It was observed that administration of the therapy in people with advanced heart failure, stimulates the production of an enzyme within the cardiac cells, enabling effective pumping and functionality by the heart.

Patients receiving a high dose of SERCA2a were found to display a significant improvement or stabilization in their heart condition after one year of receiving the therapy.

Compared to placebo, gene therapy with SERCA2a was found to largely benefit this ailing patient population. SERCA2a was found to be fairly safe with no increased evidence of adverse events, disease-related events, laboratory abnormalities, or arrhythmias.

Roger J. Hajjar, MD the Research Director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories noted that

“Few treatment options have shown such improved clinical outcomes in this patient population in the last decade.”

Arthur and Janet C. Ross Professor of Medicine, and Gene and Cell Medicine, Mount Sinai School of Medicine stated,

“This study establishes a new paradigm for the treatment of heart failure by clinically validating SERCA2a as a novel target. In addition, by showing that adeno-associated vectors are safe to use in patients with advanced heart failure, this study ushers a new era for gene therapy for the treatment of failing hearts.”

The safety and efficacy of SERCA2a was established in a randomized, double-blind, placebo-controlled study called The CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial. Thirty nine patients with advanced heart failure were enrolled in this study and were evaluated for over a year. Patients were randomized to one of the four study arms receiving either SERCA2a in one of three doses or placebo. A routine outpatient cardiac catheterization procedure was employed to deliver the therapy directly to the patient’s heart.

The patient group receiving high-dose SERCA2a therapy demonstrated improvement and/or stabilization in symptoms, overall heart function, biomarker activity, and ventricular mechanics and function. Further, these patients displayed cardiovascular hospitalizations averaging 0.4 days, which is drastically low, as compared with 4.5 days in the placebo group.

Dr. Hajjar said,

“Even though heart failure mortality has decreased over the last decade with the help of standard pharmacological and device therapies, patients with advanced heart failure continue to die at high rates. The CUPID trial offers a new therapeutic option for these patients.”

In 1999, the Mount Sinai team led by Dr. Hajjar made a pioneering discovery of the cardiac-specific target. The state-of-the-art custom built laboratories at Mount Sinai School of Medicine in New York provided the infrastructure for pursuing and exploring its landmark potential as a treatment delivered via gene therapy.

The U.S. Centers for Disease Control and Prevention have established that approximately 5.8 million Americans suffer from heart failure each year, and the number of newly diagnosed cases stands at 670,000. Of the number of people who have heart failure, 20% die within a year of being diagnosed. In 2010, the projected expenditure on heart failure in the United States is estimated to be $39.2 billion that includes the cost of health care services, medications, and lost productivity.

Although aggressive medical and device therapy is the frequently used treatment of choice for heart failure, the condition is found to have no permanent cure. Shortness of breath, tiredness, and swelling in the ankles, feet, legs, and sometimes the abdomen are the warning signs and most common symptoms used for the diagnosis of heart failure.

The CUPID Trial is funded by Celladon Corporation. The company was co-founded by Dr. Hajjar who has an equity interest in Celladon Corporation and participates on an Advisory Board.

Source
Circulation

Written by Barry Windsor