News | Stem Cell Therapies | September 04, 2015

No Benefit to Gene Transfer Therapy for Heart Failure Patients

Patients saw no reduction in recurrent events in largest gene therapy study to date for the population

CUPID 2, gene transfer therapy, heart failure patients, no benefit, ESC 2015, SERCA2a

September 4, 2015 — Gene transfer therapy to correct an enzyme abnormality involved in myocardial contraction and relaxation did not improve outcomes in heart failure patients with reduced ejection fraction, results of the CUPID 2 study show.

The findings, presented at the European Society of Cardiology (ESC) Congress 2015, represent the largest gene transfer study to date in this population.

“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,” said principal investigator Barry Greenberg, M.D., from the University of California San Diego (UCSD) Sulpizio Cardiovascular Center.

But the results provide some important information for future research in this area, he said.

“They 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,” he said.

CUPID 2 was based on the observation that deficiency of the enzyme sarcoplasmic reticulum CA2+ ATPase (SERCA2a), is linked to progression of heart failure and correction of this abnormality by gene transfer may improve cardiac function.

A pilot study by the same group showed that a single intracoronary infusion of the SERCA2a gene using an AAV vector had favorable effects in patients with advanced heart failure (Circulation 2011;124:304–13).

CUPID 2 (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b) investigated this finding further, enrolling 250 heart failure patients with reduced ejection fraction from 67 centers in the United States, Europe and Israel. 

Patients were randomized to receive one dose of either gene therapy (n=121) or placebo (n=122) and then followed for at least one year.

The primary efficacy endpoint was time to recurrent events, defined as hospitalizations or ambulatory treatment for worsening heart failure. The secondary efficacy endpoint was time to first terminal event, defined as all-cause death, heart transplant or implantation of a mechanical circulatory support device (MCSD). 

After a median follow-up period of 17.5 months, patients in the gene therapy group did not show improvements in either the primary or secondary endpoints compared to the placebo group.

Specifically, there were 104 recurrent events and 36 terminal events in the gene therapy arm compared to 128 and 29, respectively, in the placebo arm (hazard ratio [HR] 0•93, P=0•81 and HR 1•27, p=0•40 respectively). No safety issues were noted.

“Why infusion of SERCA2a did not improve outcomes in CUPID 2 is not certain and review of the data is underway to try to understand this,” said Greenberg.

“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.”

“Although deficiencies in SERCA2a activity and their correction by gene transfer have been demonstrated in animals, it is possible that these findings are not applicable in human heart failure and that raising the level of SERCA2a activity cannot alter the trajectory of the disease,” he suggested.

“Although CUPID 2 did not meet its end-points, it was an important study and the results should help inform future efforts using gene therapy to treat heart failure.”

The study was funded by Celladon Corp. Greenberg has been a consultant for and received honoraria from Celladon.

For more information: www.escardio.org

Related Content

Guideline Adherence, Not Patient Volume, May Be Better Hospital Heart Failure Metric
News | Heart Failure | February 01, 2018
February 1, 2018 –  In evaluating the quality of care given to those hospitalized with...
First-in-Man RenalGuard Studies Show Promise for Heart Failure Patients
News | Heart Failure | January 02, 2018
RenalGuard Solutions Inc. reported positive results from a first-in-man feasibility study focusing on a novel use of...
ACC Issues New Guidance to Optimize Heart Failure Treatment
News | Heart Failure | December 22, 2017
December 22, 2017 — To help streamline treatment of patients with...
Coffee Associated With Reduced Risk of Heart Failure, Stroke. AHA 2017. #AHA2017
News | Heart Failure | November 25, 2017
November 25, 2017 — Drinking coffee may be associated with a decreased risk of developing heart failure or having str
Heart failure associated with methamphetamine (meth) use has risen dramatically in recent years among U.S. veterans, according to preliminary research presented at the 2017 American Heart Association (AHA) Scientific Sessions.
News | Heart Failure | November 25, 2017
November 25, 2017 — Heart failure associated with methamphetamine (meth) use has risen dramatically in recent years a
The Corvia intra-atrial shunt to treat diastolic heart failure.

The Corvia intra-atrial shunt to treat diastolic heart failure.

Feature | Heart Failure | November 25, 2017
November 25, 2017 – Results presented at the 2017 American Heart Association (AHA) Scientific Sessions and published
Surgery Could Reduce Frailty in Adults With Heart Failure
News | Heart Failure | November 17, 2017
November 17, 2017 — Common practice, and recently published research, shows that the risk of complications with surge
News | Heart Failure | November 13, 2017
November 10, 2017 — Moderna Therapeutics announced a new license and collaboration with AstraZeneca to co-develop and
Scientists Reverse Advanced Heart Failure in Mouse Model
News | Heart Failure | October 30, 2017
October 30, 2017 — Researchers have discovered a previously unrecognized healing capacity of the heart.
Trial Data Shows Positive Predictive Results for Boston Scientific HeartLogic Heart Failure Diagnostic
News | Heart Failure | October 20, 2017
October 20, 2017 — Boston Scientific announced new data from the Multisensor Chronic Evaluation in Ambulatory Heart F
Overlay Init