No gene therapy–related serious adverse events have been reported to date across both cohorts in Medera’s Phase 1/2a MUSIC-HFpEF trial of SRD-002. In the low-dose cohort, patients showed improvements in NYHA class and Kansas City Cardiomyopathy Questionnaire at 6 and 12 months, alongside stabilizations or improvements in pulmonary capillary wedge pressure at rest and peak exercise, measured invasively. The high-dose cohort is now fully dosed and in early follow-up.
The company completed dosing of the five-patient high-dose cohort (4.50×10^13 vg per patient), marking full enrollment of Cohort B in this first-in-human HFpEF gene therapy program. SRD-002 uses an AAV1 vector delivering SERCA2a and is administered via a minimally invasive intracoronary infusion. The approach is designed to concentrate transgene delivery to myocardium and reduce total vector load relative to systemic IV gene therapy, which commonly targets 10^15–10^16 vg per patient. Dose selection was informed by Medera’s human “mini-Heart” platform and a human-relevant HFpEF disease model co-developed with AstraZeneca. The program holds IND clearance and Fast Track designation; patients will be followed for 24 months.
Strategically, this is an attempt to carve out a path in HFpEF—a heterogeneous syndrome where interventional trials have struggled—by matching a mechanistic target (calcium handling and diastolic dysfunction) with a delivery route that could mitigate systemic exposure. Intracoronary administration is both a biological and operational bet: it trades dependence on catheterization suites and interventional cardiology expertise for dose economy and potentially improved cardiac tropism. It also positions Medera away from the safety optics and manufacturing burden associated with very high-dose systemic AAV. That said, regulators and payers will remember that earlier SERCA2a gene therapy efforts in HFrEF failed to reproduce early signals in larger, controlled studies; any efficacy case in HFpEF will need to clear a higher evidentiary bar.
For sites, the model shifts execution from infusion centers to cath labs, with implications for staffing, scheduling, and training around vector handling and interventional delivery. Invasive hemodynamic assessments become central operational elements, requiring standardized rigor across centers to make exercise PCWP and related measures credible as decision-driving endpoints. CROs will need to lean on interventional cardiology networks and ensure consistent immune monitoring, vector shedding assessments, and longitudinal PRO capture. Vendors supporting pressure-wire systems, cath lab workflow, and centralized hemodynamic core labs could see increased demand. Patient selection and screening for AAV1 serostatus may constrain enrollment windows and site throughput, while vector supply and release testing remain non-trivial for any gene therapy scale-up, even at doses below systemic programs.
Near term, the key watch items are the magnitude and durability of high-dose signals through 6–12 months, concordance between invasive hemodynamics and patient-reported outcomes, and safety at the higher dose—including any immune or myocardial inflammation signals as follow-up matures. The Phase 2b design will be telling: whether Medera anchors on exercise hemodynamics, KCCQ, or a composite, and whether it runs a randomized, multicenter study powered to satisfy regulators wary of surrogate-driven narratives in HFpEF. Clarity on phenotype targeting within HFpEF, re-dosing feasibility, and manufacturing readiness will shape timelines and partnering options. If the high-dose cohort reproduces and extends the low-dose trends with clean safety, the program could move quickly; if not, the path will narrow in a field that increasingly demands robust, controlled data before embracing platform shifts like intracoronary gene therapy.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
