MUSIC-HFpEF: Encouraging first results of novel gene therapy for HFpEF

The phase 1 results of a novel gene therapy for patients with heart failure with preserved ejection fraction (HFpEF) demonstrated that the treatment did not lead to serious adverse events. The authors also reported improvements in various efficacy measures in the first patients receiving this therapy.

The phase 1/2a MUSIC-HFpEF trial (NCT06061549) evaluated the feasibility of gene therapy SRD-002, an adeno-associated virus vector (AAV1.SERRCA2a) in patients with HFpEF [1]. “Upregulation of SERCA2a as Ca²⁺ pump may lead to increased contractility, decreased ventricular arrhythmias, and a reduction in cardiac hypertrophy [2],” explained Dr Marat Fudim (Duke University, NC, USA). “The developed gene therapy is designed to achieve this target.” The therapy is delivered directly into the coronary arteries.

“In the first 5 patients treated with the novel gene therapy, intracoronary infusion of AAV1.SERCA2a as well as the accompanying invasive haemodynamic measurements were well-tolerated in the investigated patients,” stated Dr Fudim. There were no serious adverse events related to the procedure or infusion. “Also, no liver enzyme abnormalities were observed following the delivery of the treatment,” he added. In terms of efficacy, it was mentioned that most patients improved with regard to NYHA classification at 12 months and that the mean pulmonary capillary wedge pressure (PCWP) improved or remained stable. In addition, the distance achieved at the 6-minute walk test was stable or improved. Finally, somewhat mixed results were observed for NT-proBNP levels; 3 participants displayed stabilisation or improvement, whereas 2 others had a worsened NT-proBNP level.

“Clinical management of HFpEF is challenging, since there are not many effective therapies,” said Dr Fudim. “The first results of SRD-002 gene therapy are encouraging, and I’m looking forward to see more safety and efficacy data for this innovative treatment.”

1. Fudim M, et al. Gene therapy for heart failure with preserved ejection fraction. Late-breaking clinical trials in chronic heart failure, Heart Failure 2025, 17–20 May, Belgrade, Serbia.
2. Ishikawa K, et al. Circ Res. 2018;123(5):601-613

Medical writing support was provided by Robert van den Heuvel.
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Posted on 22 May 202517 July 2025