The US FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Lexeo Therapeutics' LX2020 gene therapy for PKP2-associated arrhythmogenic cardiomyopathy (ACM), following interim clinical data showing dose-dependent restoration of PKP2 protein expression and encouraging reductions in ventricular arrhythmias. LX2020 is an AAVrh10-based gene replacement therapy, while RMAT is an FDA expedited program for regenerative medicine therapies targeting serious conditions with preliminary clinical evidence of potential benefit, potentially leading to eligibility for accelerated approval, priority review, and rolling review, alongside enhanced FDA interactions during development. LX2020 now holds RMAT, Orphan Drug, and Fast Track designations.
The designation was based on interim data from the ongoing HEROIC-PKP2 Phase I/II trial, the most detailed readout of which Lexeo reported in January 2026. Across ten dosed participants, cardiac biopsy data from seven showed dose-dependent increases in PKP2 protein expression — a mean increase of 93% in the low-dose cohort and 162% in the high-dose cohorts, assessed by western blot. Among the eight participants with at least six months of follow-up as of the January 7, 2026 data cutoff, non-sustained ventricular tachycardia (NSVT) showed a 22% mean improvement in high-dose participants at the latest visit, and premature ventricular contractions (PVCs) showed a 14% mean improvement. LX2020 was generally well tolerated across all ten participants, with no clinically significant complement activation; liver function test elevations in five high-dose participants resolved with protocol-specified immunosuppression.
LX2020 delivers a functional, full-length copy of the PKP2 gene via the AAVrh10 capsid to cardiomyocytes, with the goal of restoring the desmosomal complex disrupted by loss-of-function PKP2 mutations. PKP2 mutations account for approximately 50% of arrhythmogenic cardiomyopathy (ACM) cases, and the condition is estimated to affect approximately 60,000 people in the United States. No approved disease-modifying treatments currently exist for PKP2-ACM, according to Lexeo.