Medera SRD-002 gene therapy hits 12-month HFpEF endpoints
Medera Inc. has reported 12-month results from its MUSIC-HFpEF Phase 1/2a trial, showing that eight of ten patients met a prespecified threshold for normalisation of cardiac filling pressures following a single intracoronary infusion of SRD-002, its AAV1-delivered SERCA2a gene therapy. The data were presented as a Late-Breaking Clinical Trial at the European Society of Cardiology Congress 2026 in Munich.
The primary haemodynamic finding centred on peak exercise pulmonary capillary wedge pressure, a direct invasive measure of cardiac filling that is elevated in heart failure with preserved ejection fraction. Mean PCWP fell by approximately 30% at 12 months across both dose cohorts, which the company describes as one of the largest sustained reductions in exercise filling pressure reported in an interventional HFpEF trial. Crucially, the reductions continued to deepen between the six- and twelve-month timepoints, suggesting an ongoing biological effect from a single administration.
Clinical and functional findings
Symptomatic and quality-of-life outcomes tracked the haemodynamic signal. Five of six patients who entered the trial with New York Heart Association class III symptoms improved to class II, mean Kansas City Cardiomyopathy Questionnaire scores rose by 17.8 points, and functional capacity stabilised or improved across all patients. A dose-response pattern was apparent, with the high-dose cohort (4.5x10¹³ vg, n=5) showing generally greater benefit than the low-dose group (3x10¹³ vg, n=5).
Marat Fudim, Medical Director for the Heart Failure Research Unit at Duke University Medical Center, who presented the data, said: "The magnitude and durability of the filling pressure reductions we observed, paired with meaningful improvements in symptoms and quality of life, support impaired calcium handling as a disease-defining mechanism in HFpEF and reinforce the case for advancing this approach into randomised evaluation."
Safety data remain encouraging. No treatment-related serious adverse events, dose-limiting toxicities, or treatment discontinuations were recorded across all ten patients, and no Grade 3 or higher liver enzyme elevations were observed. Medera highlighted that intracoronary delivery achieved targeted myocardial uptake at approximately 100- to 300-fold lower vector doses than systemic intravenous AAV approaches, and without routine immunosuppression, a notable differentiator given the immunogenicity concerns that have complicated AAV gene therapies in other settings.
Market context and regulatory path
HFpEF represents roughly half of the estimated 64 million global heart failure cases, yet approved therapies address symptoms and cardiovascular risk rather than the underlying myocardial dysfunction. SGLT2 inhibitors such as empagliflozin have demonstrated mortality and hospitalisation benefits and now form a pillar of HFpEF management, but no disease-modifying approach has yet reached approval. That gap has drawn considerable drug development activity, including small-molecule, biologic, and gene therapy programmes from a range of academic centres and companies targeting mechanisms including inflammation, fibrosis, and, as with SRD-002, calcium handling.
SERCA2a as a target is not new: an earlier programme, CUPID2, tested a first-generation AAV1.SERCA2a construct in heart failure with reduced ejection fraction and did not meet its primary endpoint in a larger randomised trial. Medera positions SRD-002 as a next-generation iteration with a refined vector and delivery approach, and the open-label Phase 1/2a design means the current results, while encouraging, need to be interpreted with caution ahead of randomised controlled data.
The company says the 12-month dataset supports advancement to a Phase 2b randomised trial, though a timeline, design, or regulatory interactions have not yet been announced. Medera holds FDA Fast Track designation for its HFpEF programme, which could accelerate the review process if randomised data are supportive. Investors and clinicians will be watching for trial design details and the initiation of enrolment as the next substantive catalysts.