Tenaya Therapeutics announced interim Phase 1b/2 clinical trial data for TN-201, a gene therapy for •MYBPC3•-associated hypertrophic cardiomyopathy (HCM). The data, presented at the American College of Cardiology Scientific Sessions (ACC.25), showed TN-201 was well-tolerated at the 3E13 vg/kg dose, with biopsies confirming robust transduction and RNA expression increasing over time. Notably, all three patients in the initial cohort, who had severe disease at baseline, improved to NYHA Class I (no limitations on physical activity).
This news holds substantial promise for •MYBPC3•-associated HCM patients, a population with limited treatment options and a high risk of serious complications, including heart failure, arrhythmias, and sudden cardiac death. These early results suggest that gene therapy could address the underlying genetic cause of this aggressive form of HCM, potentially altering the disease’s trajectory and improving patients’ quality of life. The improvement observed, even in patients who had already undergone myectomy and required implantable cardiac defibrillators, further underscores the potential impact of this therapy.
Key technical findings include sustained TN-201 DNA presence in the heart, robust and increasing TN-201 RNA expression, and increased MyBP-C protein levels. While some biomarker levels initially fluctuated due to immunosuppression, they returned to baseline after the drugs were discontinued. Importantly, two of the three patients experienced improvement in measures of hypertrophy, including a reduction in left ventricular posterior wall thickness and, in one patient, a decrease in left ventricular mass. The second dose cohort is currently enrolling patients at a higher dose (6E13 vg/kg), with initial data expected in the second half of 2025.
The positive early signals from this trial create optimism for the future of •MYBPC3•-associated HCM treatment. The forthcoming data from the higher dose cohort will be crucial for confirming the therapy’s efficacy and safety profile. If these positive trends continue, TN-201 could represent a significant advancement in treating this challenging genetic heart disease. The ongoing research also highlights the growing potential of gene therapies to address previously intractable conditions.
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.
