First-in-human study of TN-201, an AAV9 gene replacement therapy in <i>MYBPC3</i> -associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-1
Milind Y. Desai, Sherif F. Nagueh, John R. Giudicessi, Michael J. Previs, Danielle Kellner, Matthew J. Pollman, Fatbardha Varfaj, Laura Robertson, Natasha Sonicheva-Paterson, Richard Pushkin, Brian Mangal, LaTanya Tomlinson, W. G. Harrison, Lynn Yamamoto, Gretchen Argast, Laura M. Lombardi, Kathryn N. Ivey, Whittemore G. Tingley
Abstract
This brief report details the initial findings from a Phase 1b/2 trial of TN-201, an adeno-associated virus serotype 9 (AAV9) gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition with significant morbidity, increased risk of mortality, and no approved therapy for the majority of patients. TN-201 was well tolerated, and changes to the management of potential immune responses resulted in a shorter period of immunosuppression. These results show consistent transduction and expression of TN-201 in cardiomyocytes, corresponding with increases in MyBP-C levels, reductions or stabilization of cardiac biomarkers, and reductions in key measures of left ventricular (LV) hypertrophy.