Tenaya’s TN-201 gene therapy shows durable cardiac remodeling, symptom improvement, and functional gains in MYBPC3-associated hypertrophic cardiomyopathy, with EMA PRIME designation and FDA pediatric program support.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Tenaya Therapeutics reported new interim results from its ongoing MyPEAK-1 Phase 1b/2 trial (NCT05836259) showing that TN-201 delivered durable reductions in cardiac hypertrophy, sustained symptom improvement, and functional gains in patients with MYBPC3-associated hypertrophic cardiomyopathy (HCM).
Benefits extended up to two years after treatment in the lower-dose cohort, while patients receiving the higher dose demonstrated earlier signs of clinical improvement.
Trial Design and Disease Background
Seven patients have received TN-201 to date, with efficacy data available for six. All enrolled patients had severe nonobstructive HCM characterized by marked cardiac hypertrophy and heart failure symptoms despite standard treatment.
TN-201 is an AAV9-based gene therapy that delivers a functional MYBPC3 gene to cardiac muscle cells through a one-time intravenous infusion. The therapy aims to restore production of myosin-binding protein C (MyBP-C), addressing the underlying genetic cause of disease. MYBPC3 mutations represent the most common genetic cause of HCM, a progressive condition associated with heart failure, arrhythmias, stroke, and sudden cardiac death.
Cardiac Remodeling and Clinical Benefits
Patients in Cohort 1 (3E13 vg/kg) were followed for 78 to 104 weeks, while those in Cohort 2 (6E13 vg/kg) were followed for 26 to 52 weeks.
All six evaluable patients achieved reductions in left ventricular mass index (LVMI), a key marker of cardiac hypertrophy, and five showed reductions in ventricular wall thickness. These improvements remained durable through two years in Cohort 1, while patients receiving the higher dose experienced earlier structural responses.
Clinical benefits extended beyond cardiac remodelling. Five of six patients improved by at least one New York Heart Association (NYHA) class and are now classified as NYHA Class I. Four patients achieved clinically meaningful improvements in Kansas City Cardiomyopathy Questionnaire scores, with gains ranging from 12 to 56 points. The three evaluable patients in the higher-dose cohort recorded a mean improvement of 36 points.
Functional capacity also improved. Three patients increased six-minute walk distance by 50 to 255 meters, substantially exceeding the 30-meter threshold considered clinically meaningful. One higher-dose patient also demonstrated a meaningful improvement in peak oxygen consumption.
Biomarker and Safety Findings
Cardiac biomarkers supported the clinical findings. Troponin levels improved or remained stable in five of six patients, while NT-proBNP improved in three. Serial cardiac biopsies confirmed robust gene transfer and expression, with MyBP-C protein levels increasing by an average of 4% over time.
TN-201 remained generally well tolerated at both dose levels. Investigators reported no dose-limiting toxicities, no new treatment-related safety events, and successful discontinuation of immunosuppressive therapy in all treated patients.
Regulatory Momentum and Next Steps
The European Medicines Agency granted TN-201 PRIority MEdicines (PRIME) designation, while the U.S. Food and Drug Administration accepted the pediatric TN-201 program for biallelic MYBPC3-associated HCM into its Rare Disease Evidence Principles initiative.
According to Chief Medical Officer Whit Tingley, MD, PhD, the durability observed in Cohort 1 and the earlier responses emerging in the higher-dose cohort support the potential disease-modifying effect of TN-201.
Tenaya continues enrolling patients in the 6E13 vg/kg expansion cohort and expects to report additional long-term follow-up data in the second half of 2026 while advancing discussions with regulators on pivotal trial design.
Reference
About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.