Abstract 19470: Sustained Improvement in Clinical Outcomes with MYDICAR® Compared to Optimal Therapy 1-year after Initial Gene Therapy in Patients with Advanced Heart Failure-The CUPID Trial
Background: CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease) is a phase 2 study which compared AAV1/SERCA2a (MYDICAR®) to placebo (optimal medical therapy) in 39 stable advanced HF patients (NYHA Class III/IV, LVEF <35%, VO2 max <20 mL/kg/min) (25 active:14 placebo). This study investigated if normalizing intracellular calcium cycling with genetically targeted SERCA2 enzyme replacement would have beneficial effects in heart failure patients.
Methods: This prospective phase 2 study examined NYHA, MLWHFQ, 6MWT, VO2 max, NT-ProBNP, LVEF and LVESV, and duration of CV hospitalizations and clinical outcomes at 6 and 12 monthes. The primary efficacy endpoint was analyzed at 6-months post-dose. Additional assessment of all end points have been performed at 12 months.
Results: Study primary safety and efficacy endpoints were met in the 6-month analysis. High dose (1 × 1013 DRP) patients had substantially improved MLWHFQ, 6MWT, NT-ProBNP and LVESV results with favorable trends in AAV1/SERCA2a treated patients in VO2max, EF and NYHA. Mean duration of hospitalization was 0.2 days versus 2.1 days for high-dose vs placebo. At 9 months, high-dose patients vs placebo show significant delay in and reduced frequency of CV related clinical events (death, need for LVAD or cardiac transplant, worsening HF or HF related hospitalizations): 52% risk-reduction for high dose versus placebo, hazard ratio (CI) 0.48(0.25–0.93; P=0.030). Individual patient results are depicted in Figure 1.
Conclusions: The administration of AAV1/SERCA2a in patients with advanced heart failure results in an excellent safety profile and substantially improved clinical outcomes compared to optimal medical therapy (placebo) sustained at 1-year post-dosing. AAV1/SERCA2a treated patients (high dose) showed a 52% risk-reduction in CV related clinical events (death, need for LVAD or cardiac transplant, worsening of HF or HF related hospitalizations) vs. placebo.
- © 2010 by American Heart Association, Inc.