Heart Failure Patients: Gene Transfer Therapy Does Not Help

Barry Greenberg, MD, UCSD Sulpizio Cardiovascular Center, La Jolla, California, USA, presented results from the Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b (CUPID 2) gene transfer study at the European Society of Cardiology 2015 Congress.

Greenberg remarked, “Despite promising results from earlier studies, the therapy did not reduce either recurrent heart failure events or terminal events in the overall study population or in pre-specified subgroups.”

Based on the observation that deficiency of the sarcoplasmic reticulum CA2+ ATPase (SERCA2a) enzyme was linked to the progression of heart failure, the CUPID 2 study iassessed whether a single intracoronary SERCA2a infusion produced any favorable effects in advanced heart failure patients.

CUPID 2 involved a total of 250 heart failure patients who were randomized to receive one dose of either gene therapy or placebo and then followed for a one-year period.

The primary endpoints were defined as time to hospitalizations or ambulatory treatment for the incidences of worsening heart failure. The secondary endpoints included time to all-cause death, heart transplant, or mechanical circulatory support device (MCSD) implantation.

Results indicated there were 104 recurrent events and 36 terminal events in the group administered gene therapy compared with 128 recurrent events and 29 terminal events in the placebo group.

“Although preliminary results in experimental models and in pilot studies of heart failure patients showed favorable results, it is possible that SERCA2a may not be an appropriate target for treating heart failure in human patients, and that the positive pilot study results could just be a chance finding,” said Greenberg.

Considering future studies, Greenberg said these results "demonstrate that clinical trials testing gene transfer can be carried out effectively in heart failure patients, and that using intracoronary delivery of an adeno-associated virus (AAV) vector at this dose is safe.”