June 16, 2026 —
Pooled data from two open-label dose-escalation studies suggest that AAVrh.10hFXN, an investigational AAV-based gene therapy encoding normal human frataxin, may improve key cardiac measures in patients with Friedreich’s ataxia cardiomyopathy. The results were published in JAMA Cardiology.
The pooled analysis included 17 patients from a Phase 1A investigator-initiated trial at Weill Cornell Medicine and a Phase 1/2 industry-sponsored trial by Lexeo Therapeutics, where the therapy is being developed as LX2006. The studies primarily evaluated safety, with exploratory endpoints including left ventricular mass index, or LVMI, high-sensitivity cardiac troponin I, or hs-cTnI, and cardiac frataxin protein expression after systemic AAV delivery.
Friedreich’s ataxia is caused by pathogenic GAA trinucleotide repeat expansions in the FXN gene, which reduce production of frataxin, a mitochondrial protein required for normal cellular energy metabolism. Cardiomyopathy is a major cause of morbidity and mortality in FA, accounting for approximately 60% to 65% of deaths. While omaveloxolone is approved for neurologic manifestations of FA, no therapy is currently approved specifically for FA cardiomyopathy.
AAVrh.10hFXN is designed to deliver a functional human frataxin gene through intravenous administration. Three dose levels were evaluated: 1.8×10¹¹, 5.6×10¹¹, and 1.2×10¹² vector genomes per kilogram. Among eight patients who underwent cardiac biopsy three months after infusion, all showed increased cardiac frataxin protein expression. Mean cardiac frataxin increases were 20%, 81%, and 123% across the three dose cohorts, respectively.
Exploratory cardiac imaging data also showed encouraging trends. LVMI improved qualitatively in 9 of 17 patients and stabilized in the remaining eight. In a linear mixed-effects model excluding one patient who developed myocarditis at month 12, LVMI declined at a mean rate of −0.50 g/m² per month, consistent with potential structural remodeling.
Biomarker findings were directionally consistent with the imaging results. hs-cTnI, a marker of ongoing cardiac muscle injury, declined by at least 10% in 15 of 17 patients. Modeling excluding the myocarditis case estimated a mean monthly reduction of −13.7 ng/L, suggesting reduced ongoing myocyte injury after treatment.
The therapy was generally well tolerated. Four serious adverse events were reported, including one case of asymptomatic myocarditis at month 12 that was considered possibly vector-related and resolved with corticosteroids. Three additional serious events were considered possibly related to prednisone immunosuppression. No deaths, treatment withdrawals, prominent hepatotoxicity, or significant complement activation were observed.
The findings remain preliminary, given the small patient population, nonrandomized design, absence of a contemporaneous control group, and predominance of patients with early-stage cardiac disease. However, the results support further clinical development of AAVrh.10hFXN/LX2006 as a potential disease-modifying therapy for FA cardiomyopathy.
The data also help support the rationale for Lexeo’s broader LX2006 development program, including pivotal evaluation focused on cardiac endpoints such as LVMI. If confirmed in larger controlled studies, systemic AAV-mediated frataxin gene delivery could represent an important therapeutic advance for patients with Friedreich’s ataxia cardiomyopathy.
