Tenaya Therapeutics has been cleared by the independent Data and Safety Monitoring Board (DSMB) to proceed with a higher dose cohort in the MyPeak-1 phase 1b clinical trial (NCT05836259) evaluating TN-201, an investigational adeno-associated virus (AAV)-vector based gene therapy for hypertrophic cardiomyopathy (HCM) caused by mutations in the MYBPC3 gene.
The DSMB's decision was based on early safety data from the first cohort of three patients, who received a dose of 3x10^13 vg/kg of TN-201. Tenaya reported no unexpected events or toxicities related to the gene therapy in these patients. Consequently, the company has been authorized to dose patients in the second cohort at 6x10^13 vg/kg and is actively enrolling participants.
MyPeak-1 Trial Modifications
Tenaya has implemented several modifications to the MyPeak-1 protocol. These include the addition of a baseline biopsy, greater flexibility in the timing of post-treatment biopsies, expansion of eligibility to include patients with obstructive HCM and those without an implantable cardioverter defibrillator (ICD), and an increase in the potential number of participants in the dose expansion phase to 24.
According to Whit Tingley, MD, PhD, Tenaya’s chief medical officer, “The MyPEAK-1 study of TN-201 is primarily intended to establish the safety profile of TN-201 gene therapy, and we are pleased to report that TN-201 has an appropriate tolerability profile at the 3x10^13 vg/kg dose without unexpected adverse reactions.”
Trial Endpoints and Future Data
The primary endpoint of MyPeak-1 is the safety and tolerability of TN-201, assessed by the number and severity of adverse events (AEs) during the study and the number of serious AEs related to the gene therapy. The secondary endpoint is the change from baseline to 52 weeks post-treatment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Tenaya anticipates reporting detailed findings from the first cohort, including safety and tolerability data, cardiac biopsy analyses, and cardiac biomarker data, in December 2024.
