Patient Dosing Complete for Part 1 of Gene Therapy Trial in Friedreich Ataxia Cardiomyopathy


The 52-week, dose-ascending trial will have data read out in the first half of 2024, with long-term safety and efficacy evaluated over a 5-year period following completion of the initial trial.

R. Nolan Townsend, chief executive officer, Lexeo Therapeutics

R. Nolan Townsend

According to a recent announcement, patient dosing in the first cohort of the SUNRISE-FA study (NCT05445323), a phase 1/2 trial assessing LX2006 (Lexeo Therapeutics), an adeno-associated virus (AAV) gene therapy, in patients with friedreich ataxia (FA) cardiomyopathy, has completed. The first patient in the second dose cohort of the trial has commenced as well.1

SUNRISE-FA, an ongoing, dose-ascending, open-label trial, includes approximately 9 individuals with FA-associated cardiomyopathy who are followed for a 52-week period. Thus far, preliminary data from the first dose cohort indicated that the therapy was well tolerated, with no unexpected events or toxicities.

"New treatment approaches, like LEXEO’s LX2006 gene therapy candidate, are critical for individuals and caregivers confronted with the debilitating realities of FA," Jennifer Farmer, chief executive officer, Friedreich’s Ataxia Research Alliance, said in a statement.1 "Cardiomyopathy is the leading cause of death in individuals diagnosed with FA, so we are incredibly encouraged by the work that LEXEO has undertaken to try to address this life-threatening complication through gene therapy. We are grateful to all the individuals in the FA community who volunteer and participate in research studies and clinical trials."

FA is a rare, autosomal recessive disease caused by a mutation in the autosomal frataxin (FXN) gene. Currently, there is no approved therapy that alters the progression of cardiomyopathy in FA, which is responsible for 59% of FA-related deaths. LX2006, administered as a one-time infusion, is designed to target the cardiac manifestations of FA by delivering functional FXN gene to promote the expression of the frataxin protein and restore mitochondrial function in myocardial cells.

The 3 cohorts of the trial will assess LX2006 in low, mild, and high doses, with safety, as demonstrated through treatment-emergent adverse events (TEAEs) and treatment-emergent serious events, as the primary outcome. Patients included in the trial are between 18 and 40 years of age, have a confirmed genetic diagnosis of FA, and met protocol specified ranges for antibodies and measures for FA cardiomyopathy. Those with uncontrolled diabetes, abnormal liver function, active infection of any time, and a contraindication to cardiac MRI, were excluded from the study.2

READ MORE: Continued Improvements With Risdiplam Seen in 4-Year Analysis of FIREFISH

"The advancement of SUNRISE-FA helps pave the way for a potential life-altering treatment for patients with FA cardiomyopathy. Because no approved therapy has been shown to treat the cardiac manifestations of FA, a significant unmet need persists for these patients," R. Nolan Townsend, chief executive officer, Lexeo Therapeutics, said in a statement.1 "We look forward to continuing to progress this program with data readouts expected in the first half of 2024."

The cardiac involvement seen in FA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and dilated cardiomyopathy. Dilated cardiomyopathy and arrythmia are associated with mortality in patients with FA, whereas hypertrophic cardiomyopathy is not.3

In 2014, a consensus statement for the multidisciplinary treatment of patients with FA recommended that electrocardiogram and echocardiography should be performed at the initial presentation and that patients should be referred to a cardiologist only for cardiac symptoms or abnormal cardiac testing. Cardiac MRIs, which can detect remodeling and decreased myocardial perfusion reserve, may be a useful tool in the early detection of disease and/or monitoring the therapeutic response.

1. Lexeo Therapeutics announces completion of first cohort and dosing in second cohort in SUNRISE-FA, a phase 1/2 clinical trial of LX2006 for the treatment of Friedreich’s ataxia cardiomyopathy. News release. Lexeo Therapeutics. June 13, 2023. Accessed July 18, 2023.
2. Gene therapy for cardiomyopathy associated with Friedreich’s ataxia. Updated May 10, 2023. Accessed July 18, 2023.
3. Hanson E, Sheldon M, Pacheco B, Alkubeysi M, Raizada V. Heart disease in Friedreich’s ataxia. World J Cardiol. 2019;11(1):1-12. doi:10.4330/wjc.v11.i1.1
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