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Gene Therapy to be Assessed in Heart Failure With Preserved Ejection Fraction Trial

SRD-001 is designed to increase expression and functional activity of SERCA2a, down-regulation of which is associated with all forms of heart failure.

Sardocor Corp, a gene therapy subsidiary of Medera Biotherapeutics, has received investigational new drug (IND) clearance from the FDA for SRD-001 for the potential treatment of heart failure with preserved ejection fraction (HFpEF).

“The unique ability of SRD-001 to enhance ventricular relaxation, a critical mechanism of the diastolic dysfunction known to commonly occur in the stiff hearts of HFpEF patients, presents a novel, exciting and physiologically-based approach to a condition the treatment of which has eluded researchers for decades. In MUSIC-HFpEF1, efficacy assessment is based on rigorous screening and follow-up of potential subjects with exercise hemodynamics and gas exchange as well as echocardiographic, clinical and biomarker metrics in this open-label study.” Jonathan Plehn, MD, chief medical officer, Sardocor, said in a statement.

SRD-001 is an adeno-associated virus (AAV) therapy 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.The therapy will be evaluated in the newly initiated phase 1b/2a Modulation of SERCA2A In Cardiomyopathy (MUSIC)-HFpEF trial.

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“This clinical trial will serve to validate the large body of work that has implicated deficiency of SERCA2a in HFpEF and is a landmark achievement for Medera/Sardocor which is committed to treating HFpEF patients with a single infusion of SRD-001. The initiation of the First-in-Human MUSIC-HFpEF1 trial of SRD-001 also extends Sardocor’s cardiac gene therapy portfolio to a disease state with a large unmet need,” Roger Hajjar, MD, scientific cofounder, Medera and Sardocor, added to the statement.

Patients with HFpEF, confirmed by rigorous exercise hemodynamics and gas exchange, will be enrolled in the open-label, dose-escalation, 52-week MUSIC-HFpEF trial. The trial will primarily assess safety of intracoronary SRD-001 infusion and will also assess clinical efficacy with what Sardocor termed “cutting-edge” approaches.

Another of Medera’s subsidiaries, Novoheart, recently announced the successful generation of the first bioengineered HFpEF human heart models to reproduce key HFpEF characteristics, jointly with AstraZeneca. This allowed Novoheart to identify the downregulation of SERCA2a as a major cause of calcium-handling defects in HFpEF, which in turn has further supported the proof-of-concept of the MUSIC-HFpEF trial. Accordingly, preclinical models have shown that AAV-mediated overexpression of SERCA2a in HFpEF human heart models reverses relaxation defects and other disease phenotypes, and animal models have demonstrated that SERCA2a activation leads to enhanced relaxation. SERCA2a downregulation has been universally demonstrated in all forms of heart failure.

“Given the central importance of SERCA2a in multiple cardiovascular diseases, we are also investigating the use of SRD-001 for treating other indications,” Ronald Li, PhD, chief executive officer and founder, Medera, added.

REFERENCE
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. https://www.einnews.com/pr_news/602028511/medera-receives-fda-clearance-for-a-first-in-human-gene-therapy-trial-for-heart-failure-with-preserved-ejection-fraction