お知らせ • Oct 18
Tenaya Therapeutics, Inc. Announces Updates on TN-201 Gene Therapy Program for MYBPC3-associated HCM
Tenaya Therapeutics, Inc. shared updates related to its ongoing Phase 1b/2 MyPEAK-1 clinical trial of TN-201. TN-201 is being developed for the potential treatment of MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). TN-201 gene replacement therapy is designed to increase protein levels of MyBP-C to slow or even reverse the course of disease by delivering a functional copy of the MYBPC3 gene to heart muscle cells. Tenaya completed dosing of the first three patients (Cohort 1) at the 3E13 vg/kg dose in the MyPEAK-1 trial with no unexpected events or toxicities associated with study drug observed. Safety data from Cohort 1 were reviewed by an independent Data and Safety Monitoring Board (DSMB), showing a safety and tolerability profile consistent with other AAV gene therapies at this dose. Accordingly, the DSMB recommended that Tenaya proceed with dose escalation to the 6E13 vg/kg dose (Cohort 2), per protocol. Enrollment of Cohort 2 is underway. Tenaya has implemented several changes in the MyPEAK-1 protocol intended to support future development, including: Adding a baseline biopsy, increasing the total number of cardiac biopsies from two to three, and permitting more flexible timing of post-dose biopsies to help characterize TN-201 expression over time; Expanding eligibility to include participants who do not have an implantable cardioverter defibrillator device (ICD) and to permit adults with either obstructive or nonobstructive forms of HCM to enroll and Increasing the potential number of total patients enrolled in the dose expansion portion of the clinical trial from nine to twenty-four adults. Tenaya plans to report initial data from Cohort 1 in December of this year. This readout is expected to focus on TN-201’s safety and tolerability, analyses of cardiac biopsy, as well as changes from baseline in cardiac biomarkers. The MyPEAK-1 clinical trial is also collecting data to understand TN-201’s effect on imaging biomarkers, heart function, exercise capacity, functional status, and patient quality of life. As part of Tenaya’s ongoing efforts to characterize the disease burden for children and adolescents with MYBPC3-associated HCM, Dr. Tingley recently presented data from a study conducted in partnership with the Sarcomeric Human Cardiomyopathy Registry (SHaRe): Of the nearly 1,800 MYBPC3-associated HCM individuals identified in SHaRe’s database, approximately 13% were diagnosed prior to age 18. The cumulative lifetime risk of severe events for MYBPC3-associated pediatric patients is very high, with 50% experiencing significant morbidity by age 40. Both adult and pediatric MYBPC3-associated HCM individuals have high rates of serious complications, such as heart failure and ventricular arrhythmias, highlighting the need for timely diagnosis, active monitoring and new genetic medicines that can have a meaningful impact on outcomes. Tenaya also continues to characterize the pediatric MYBPC3-associated HCM population through the MyClimb natural history study (Clinicaltrials.gov ID: NCT05112237) with more than 200 children and adolescents enrolled across 29 sites in USA, Canada, Spain, and the United Kingdom. About the MyPEAK-1 Phase 1b/2 Clinical Trial: The MyPEAK-1 Phase 1b/2 clinical trial is an ongoing, multi-center, open-label, dose-escalating study designed to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201 gene replacement therapy. The trial is enrolling symptomatic (New York Heart Association Class II or III) adults who have been diagnosed with MYBPC3-associated HCM. MyPEAK-1 is testing doses of 3E13 vg/kg and 6E13 vg/kg in two cohorts of three patients each. Following DSMB assessment of safety at each dose, planned dose expansion cohorts may enroll up to 24 MYBPC3-associated HCM adults with either nonobstructive or obstructive forms of HCM. About MYBPC3-Associated Hypertrophic Cardiomyopathy Variants in the Myosin Binding Protein C3 (MYBPC3) gene are the most common genetic cause of hypertrophic cardiomyopathy (HCM), accounting for approximately 20% of the overall HCM population, or 120,000 patients, in the United States alone. MYBPC3-associated HCM is a severe and progressive condition affecting adults, teens, children and infants. Mutations of the MYBPC3 gene result in insufficient expression of a protein, called MyBP-C, needed to regulate heart contraction. The heart becomes hypercontractile and the left ventricle thickens, resulting in symptoms such as chest pain, shortness of breath, palpitations and fainting. Patients whose disease is caused by MYBPC3 mutations are more likely than those with non-genetic forms of HCM to experience earlier disease onset and have high rates of serious outcomes, including heart failure symptoms, arrhythmias, stroke and sudden cardiac arrest or death. There are currently no approved therapeutics that address the underlying genetic cause of HCM. About TN-201: TN-201 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion, increasing MyBP-C protein levels to address the underlying cause of MYBPC3-associated HCM with the aim of halting or even reversing disease after a single dose. The U.S. Food and Drug Administration has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations. TN-201 has also received orphan medicinal product designation from the European Commission.
