Lexeo’s Gene Therapy LX2006 Reduces Abnormal LVMI in Patients With Friedreich Ataxia Cardiomyopathy
The data come from patients treated across 2 studies.
Lexeo Therapeutics’ LX2006, an adeno-associated virus (AAV) vector-based gene therapy, has demonstrated the ability to reduce left ventricular mass index (LVMI) in patients with Friedreich ataxia (FA) cardiomyopathy who had a normal LVMI at baseline.1
The data come from patients treated across 2 studies: the Lexeo phase 1/2 SUNRISE-FA clinical trial (NCT05445323) and the phase 1a Weill Cornell Medicine investigator-initiated trial (NCT05302271). For the 6 patients across these studies who had an abnormal LVMI as baseline, 5 of the patients showed an improvement of more than 10% by 12 months posttreatment. In addition, at their most recent follow-up visit, 5 of the 6 patients have shown an LVMI within the normal range, as of a March 25, 2025 data cutoff. Lexeo reported that the mean improvement in LVMI for the 6 patients was 27% as of the latest follow-up visit and that a mean improvement of 25% in LVMI was seen by the 12-month posttreatment visit or sooner. Furthermore, it was noted that for the patients treated in the middle and high dose level cohorts, greater improvement was seen at earlier time points in comparison to patients who received the low dose, indicating a dose-dependent response. For the 6 patients in the studies who had a normal LVMI at baseline, most showed stabilization or improvement of LVMI over time.
Lexeo also reported that among 12 patients treated across both studies, 10 showed a decrease in lateral wall thickness at their latest visit and 11 showed more a greater than 25% decrease in high-sensitivity troponin I levels at their lates visit. In addition, improvements in functional measures, such as the modified Friedreich Ataxia Rating Scale and the Kansas City Cardiomyopathy Questionnaire, were recorded in the majority of patients.
The SUNRISE-FA additionally measured cardiac frataxin expression, a metric that was not tracked in the Weill Cornell Medicine study. It was found that at 3 months posttreatment, 8 of 8 patients (100%) in SUNRISE-FA showed increases in frataxin protein expression and that on average, dose-dependent increases were seen across the dose-level cohorts. For the 4 patients treated in the high-dose cohort, a 115% mean increase in frataxin protein expression was observed.
“These data provide strong evidence that LX2006 is acting as a beneficial disease-modifying treatment candidate, supporting its continued development as a potential first- and best-in-class therapy for FA cardiomyopathy,” Eric Adler, MD, the chief medical officer and head of research at Lexeo Therapeutics, said in a statement.1 “Cardiac dysfunction is the leading cause of death for people with FA, and the clinical and functional improvements we’ve observed across these studies could be transformational to the standard of care. Participants have experienced clinically meaningful improvements across multiple measures, as well as increased frataxin expression in the heart, all of which underscore the potential of LX2006 to positively impact outcomes for people with FA cardiomyopathy.”
The safety set included 16 patients treated across both studies. Lexeo characterized treatment with the gene therapy product as “generally well tolerated.” There were no serious adverse events assessed as grade 3 or higher. In addition, no indications of complement activation, immunogenicity, or frataxin over-expression in cardiac tissue were observed. A grade 2 case of asymptomatic myocarditis, deemed possibly related to the treatment, was reported in a patient at 1 year post-dosing. Lexeo noted that no patients discontinued participation in the studies.
Lexeo plans to carry out a registrational clinical trial for LX2006 that will utilize frataxin protein expression and LVMI as primary end points. The company anticipates that the study will launch early next year and that efficacy data may be announced in 2027. In addition, Lexeo plans to carry out a prospective natural history study for use as an external control arm for the registrational study. The company anticipates that the natural history study will start enrolling patients before the end of the second quarter of 2025.
“We believe these data show LX2006 exceeding the thresholds aligned with the FDA to support accelerated approval in the planned registrational study,” Sandi See Tai, the chief development officer at Lexeo, added to the statement.1 “We are eager to advance this promising candidate as quickly as possible to support adults and children living with the devastating and fatal impacts of FA cardiomyopathy, and we expect to initiate a registrational study by early 2026. I would like to thank the participants, caregivers, and investigators who have helped to advance this important research.”
Lexeo also has a gene therapy in its pipeline for another type of cardiomyopathy, arrhythmogenic cardiomyopathy.2 The therapy, LX2020, is currently being evaluated in a first-in-human trial after the FDA cleared its investigational new drug application in August 2023.
The company is also developing LX1001, an AAV vector-based gene therapy intended to treat patients with APOE4 homozygote Alzheimer disease (AD).3 Interim data from a phase 1/2, open-label clinical trial (NCT03634007) evaluating LX1001 were recently presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain. The results showed a dose- and time-dependent impact on apolipoprotein (APOE2) expression in patients with APOE4 homozygote AD.
