Sardocor’s Heart Failure Gene Therapy SRD-001 Garners Fast Track Designation as First Patients Are Dosed


The first 3 participants in the MUSIC-HFpEF trial have now been dosed with the AAV vector-based gene therapy.

Roger Hajjar, MD, the director of the Mass General Brigham Gene and Cell Therapy Institute

Roger Hajjar, MD

Medera subsidiary Sardocor’s SRD-001, an investigational adeno-associated virus (AAV) vector-based gene therapy being evaluated for the treatment of Heart failure with preserved ejection fraction (HFpEF) in the phase 1/2a MUSIC-HFpEF clinical trial (NCT06061549), has been granted fast track designation by the FDA.1 In addition, the first 3 participants in the trial have now been dosed with the gene therapy.

SRD-001 is directly delivered to cardiac ventricular muscle cells by use of Sardocor’s proprietary intracoronary infusion system that is designed to increase the protein expression and functional activity of SERCA2a. In preclinical research conducted with Medera subsidiary Novoheart’s bioengineered HFpEF Human mini-Heart models, downregulated SERCA2a protein levels were implicated as the key factor in disease-associated calcium-handling defects. SRD-001 is expected to improve relaxation defects in HFpEF via overexpression of SERCA2a protein. Sardocor’s intracoronary infusion system allows for lessened dependence on tropism and for viral titers less than 1/100-fold per patient than seen in other conventional methods of administering gene therapy; this is expected to reduce or eliminate some potential adverse events while still allowing for efficient transduction.

“The enrollment of the first patients in this gene therapy trial will serve to validate the large body of work that has implicated deficiency of calcium cycling in HFpEF”, Roger Hajjar, MD, cofounder of Medera and Sardocor and the director of the Mass General Brigham Gene and Cell Therapy Institute, said in a statement.1

The open-label, dose-escalation MUSIC-HFpEF trial will seek to enroll up to 10 participants aged 50 years and older. Patients will be treated at a fixed dose of 3x1013 viral genomes. The primary end point is the change in pulmonary capillary wedge pressure measured at 24 weeks posttreatment and 52 weeks posttreatment. Resting and exercise hemodynamics, exercise tolerance, lusitropic parameters, chamber sizes, quality of life, and biomarkers will also be assessed in the study. The investigational new drug application for MUSIC-HFpEF was cleared by the FDA in November 2022.2

“Using Novoheart’s unique Human mini-Heart® platform, we are also able to titrate and optimize the dosages for human heart transduction using Sardocor’s clinical-grade AAV vector, SRD-001, which was impossible before,” Kevin Costa, PhD, the chief scientific officer and cofounder of Novoheart, added to the statement.1 “In accordance with the FDA Modernization Act 2.0, these informative preclinical human-based data were included in Sardocor’s successful IND and FTD applications for FDA regulatory approval,” said Kevin Costa, PhD, CSO and co-founder of Novoheart, a solely owned subsidiary of Medera.

CGTLive® recently spoke to Hajjar more generally about the potential of gene therapy in cardiology at the American Heart Association’s (AHA) Scientific Sessions 2023, held November 10-13 in Philadelphia, Pennsylvania. Hajjar discussed the history of gene therapy efforts and the need to continue to pioneer new vector types and delivery methods in order to improve specificity and safety.

“We've seen in [noncardiac gene therapy] trials that there's been a lot of adverse events based on the massive doses that have to be given with adeno-associated virus vectors,” Hajjar told CGTLive. “With the emergence of novel, more cardiotropic vectors and minimally-invasive techniques to deliver locally, we are now able to deliver much lower amounts of vector—100 times less. That will basically allow us to have a safer vector when we deliver these next generation capsids.”

1. Medera’s Sardocor announces fast track designation & dosing of 3 patients in first-in-human gene therapy clinical trial. News release.Sardocor Corp. February 14, 2024. Accessed February 15, 2024.
2. Medera receives FDA clearance for a first-in-human gene therapy trial for heart failure with preserved ejection fraction. News release. Medera Biopharmaceutical. November 18, 2022. Accessed February 15, 2024.
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