LX2006 is an AAV-based gene therapy candidate designed to intravenously deliver a functional frataxin gene, for the treatment of Friedreich’s ataxia cardiomyopathy (FA cardiomyopathy). Information on both the Lexeo and Weill Cornell trials can be found here.
The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.
Several laboratories investigated the efficacy of gene therapy to rescue the cardiac changes seen in mouse models. Dr. Helene Puccio’s laboratory demonstrated that an AAV delivered FXN gene rescued the FXN cardiac specific genetic knock out mouse. Dr Ron Crystal at Weill Cornell Medicine also studied adeno associated virus serotypes in cellular and animal model systems.
Dr. Crystal published several papers on AAVrh.10 serotype showing good CNS expression of the transgene payload which formed the basis for the program at Lexeo.
AAVrh.10hFXN is a nonhuman primate-derived serotype rh.10 capsid with a constitutive promoter driving the normal human frataxin cDNA. AAVrh.10hFXN is administered intravenously, a vector and route which in experimental animal models effectively delivers genes to the heart. Based on preclinical efficacy data in two murine models, intravenous AAVrh.10hFXN reverses the consequences of FA cardiomyopathy.
2022: Dr. Crystal opened an IND to study AAVrh.10hFXN gene therapy for the cardiomyopathy of Friedreich’s Ataxia.
February 16, 2022: Lexeo announced approval of their Investigational New Drug (IND) application for LX2006, an AAV-based gene therapy candidate for Friedreich’s Ataxia cardiomyopathy.
July 2022: LEXEO initiated an open-label, dose-escalation Phase 1/II clinical trial of LX2006 in patients with FA cardiomyopathy.
June 2023: Lexeo announced the completion of the first dose cohort and the dosing of the first patient in the second dose cohort in SUNRISE-FA, a Phase 1/II clinical trial of LX2006 in patients with Friedreich’s ataxia (FA) cardiomyopathy.
April 2024: Lexeo and Weill Cornell agreed to grant Lexeo a license to current and future clinical data from the Dr. Ron Crystal’s ongoing investigator-initiated Phase 1A trial of AAVrh.10hFXN to treat FA cardiomyopathy.
July 2024: Lexeo shared interim clinical data from the SUNRISE-FA Phase 1/2 clinical trial for the treatment of Friedreich ataxia cardiomyopathy (NCT05445323) and the Weill Cornell Medicine investigator-initiated Phase 1A trial (NCT05302271) (from 8 participants with > 6-months of follow-up). Among the participants with elevated left ventricular mass index (LVMI) at baseline, mean reduction in LVMI was 11.4% at 12 months (n=4) and 18.3% at 18 months (n=2). They also reported sustained and consistent improvements in other key measures of cardiac status, including left ventricular wall thickness (n=6) and troponin I (n=5), in majority of participants at 12 months. In those in the Lexeo study, an increased post-treatment frataxin expression above baseline was seen in the myocardial biopsies. In addition, LX2006 was well tolerated with no treatment-related serious adverse events to date. The next step for the SUNRISE-FA Phase 1/2 clinical trial is proceeding to Cohort 3; one participant was dosed in this cohort at the time of the presentation.
March 2025: Following a meeting with the U.S. Food and Drug Administration (FDA), Lexeo reported alignment on elements of the accelerated development pathway including:
The company also plans to provide a mid-year clinical update from the ongoing Phase I SUNRISE-FA and Weill Cornell clinical trials with safety and tolerability data, pre- and post-treatment cardiac frataxin protein expression, and clinical biomarker data for patients with more than 6 months of follow up.
To date, LX2006 has been well tolerated with no new treatment-related serious adverse events reported.
This brief video serves as an introduction to gene therapy for FA. The aim of this video and accompanying educational resources is to provide information to help individuals and families make informed decisions regarding participation in clinical trials exploring investigational drugs or gene therapy.
