Tenaya Therapeutics announced interim data from its RIDGE natural history study of adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the Plakophilin 2 (PKP2) gene. The study, the largest of its kind, is evaluating the clinical characteristics and medical history of participants, and testing for preexisting neutralizing antibodies to AAV9, the delivery vector for Tenaya’s investigational gene therapy, TN-401. The data reveals a high disease burden and potential eligibility of many ARVC patients for TN-401.
This information is crucial for understanding the unmet need in •PKP2•-associated ARVC. Current standard-of-care treatments, including medications, ablation, and implantable cardioverter-defibrillators, do not address the underlying genetic cause of the disease and appear insufficient to prevent disease progression or manage the high burden of arrhythmias. This highlights the urgency for novel therapies like TN-401, which aims to modify the disease course by delivering a functional PKP2 gene directly to heart muscle cells.
The interim RIDGE data, from 144 adult participants, showed that 83% experienced frequent premature ventricular contractions (PVCs), a marker for increased risk of life-threatening arrhythmias. Nearly half reported a history of ventricular tachycardia. Despite standard treatments, 60% of participants with available MRI data showed disease progression, indicating the ineffectiveness of current approaches to halt structural heart damage. Importantly, 93% of patients had low AAV9 neutralizing antibody titers, suggesting that the majority would be eligible for AAV9-based gene therapy like TN-401. A significant number of RIDGE study participants meet the criteria for Tenaya’s ongoing Phase 1b RIDGE-1 clinical trial, which is evaluating the safety, tolerability, and activity of TN-401.
The interim RIDGE data reinforce the significant unmet medical need in •PKP2•-associated ARVC and supports the continued development of TN-401 gene therapy. The findings provide valuable insights into the disease’s natural progression and support the potential for gene therapy to address the root cause of ARVC and improve patient outcomes. Data from the first cohort of the RIDGE-1 trial, expected in the second half of 2025, will be critical in determining the safety and potential efficacy of TN-401 in this patient population. The RIDGE study may also serve as a valuable control arm for the RIDGE-1 trial, facilitating the assessment of TN-401’s efficacy.
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.
