CUPID 2: A Phase 2b Trial Investigating the Efficacy and Safety of the Intracoronary Administration of AAV1/SERCA2a in Patients with Advanced Heart Failure

Despite use of optimised guideline-directed therapies, heart failure (HF) patients often experience worsening of their condition, recurrent hospitalizations and premature mortality. Molecular studies have identified that a deficiency in the sarco-endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) enzyme in cardiomyocytes impairs cardiac relaxation and contractility. In animal models of HF, increasing SERCA2a expression by genetic enzyme replacement therapy improves cardiac function and survival. In patients, the phase 2a CUPID 1 trial reported that SERCA2a enzyme replacement with a novel recombinant adeno-associated viral vector containing human SERCA2a cDNA (AAV1/SERCA2a) promoted reverse left ventricular remodelling and improved symptoms, functionality and the clinical course.