Interim results from Medera’s MUSIC-HFpEF Phase 1/2a study reported no gene therapy–related serious adverse events among 10 treated patients, with early signals across functional and hemodynamic measures. Five low-dose patients who completed 12 months 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; five high‑dose patients have 6–12 months of follow‑up. The data were presented as a late-breaker at AHA 2025.
The core development is the first-in-human evaluation of SRD‑002, a one-time AAV1 vector delivering cardiac SERCA2a via a proprietary intracoronary infusion. The program uses dose levels of 3.0E13 and 4.5E13 vg—higher than earlier cardiac AAV efforts yet materially below systemic IV exposures—supported by Medera’s human “mini-Heart” platform. Enrollment has been completed, the FDA has granted Fast Track designation, and the company has indicated its readiness to advance into Phase 2 to test durability and disease-modifying potential in HFpEF.
Strategically, Medera is attempting to reopen the cardiac gene therapy lane by pivoting SERCA2a toward a phenotype in which impaired relaxation and diastolic stiffness are central to the pathology. The move contrasts with the field’s current pharmacologic paradigm in HFpEF, which has delivered incremental gains with SGLT2 inhibitors but little evidence of structural modification. The choice of intracoronary delivery signals a bet on targeted myocardial transduction while containing systemic exposure—a lesson from prior cardiac AAV programs that struggled to balance dose intensity with safety and manufacturability. The company’s emphasis on human-derived in vitro modeling to tune dose and delivery is also aligned with regulators’ growing openness to non-animal translational models. However, it will still need to be translated into controlled clinical efficacy.
For sites and CROs, the operational footprint is significant. Intracoronary infusion anchors this program in cath labs with advanced heart failure capability, and the endpoints used to date—NYHA, KCCQ, and exercise hemodynamics—require tight standardization of right-heart catheterization procedures and consistent exercise protocols to reduce noise. HFpEF phenotyping and enrichment remain gating factors; neutralizing antibodies to AAV1 may drive screen failures and complicate site-level planning, and immunogenicity monitoring, vector shedding, and steroid use protocols will add layers to data collection and training. CROs with gene therapy infrastructure and cardiac procedural oversight will be advantaged, while vendors supporting centralized hemodynamic core labs and patient-reported outcomes will be pivotal to signal detection. Regulators will focus on durability, correlation between transgene expression and the program’s long-term follow-up plan, as is typical for AAV therapies.
The next inflection is Phase 2 design. To move beyond mechanistic promise, the program will likely need a randomized, sham-controlled study to control for placebo and procedural effects, with a prespecified primary endpoint that can withstand regulatory scrutiny—exercise PCWP, peak VO2, or a validated KCCQ threshold, ideally coupled with hospitalization signals. Durability beyond 12 months, neutralizing antibody dynamics, and consistency across HFpEF sub-phenotypes will determine generalizability. Manufacturing scale, lot-to-lot potency assays, and catheter-delivery reproducibility across a broader site network are practical risks. Watch for details on control strategy, enrichment criteria, and global regulatory engagement; absent hard outcomes, the credibility of a disease-modifying claim will hinge on the coherence of functional, hemodynamic, and biomarker data across a larger, well-controlled cohort.
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.
