Gene Therapy Shows Promise for Fatal Heart Condition Tied to Friedreich Ataxia

An experimental gene therapy from Lexeo Therapeutics may provide a new treatment option for Friedreich ataxia (FA) cardiomyopathy, a rare and often fatal heart complication tied to the neurodegenerative disorder.

Interim results from two early-stage studies suggest the therapy not only boosts production of a crucial mitochondrial protein but also meaningfully improves heart function, the company said in a news release.

Lexeo aims to start a registrational trial next year for LX2006, which is an adeno-associated virus (AAV) gene therapy. AAV is a non-disease-causing virus that is used as a vector to deliver a gene therapy to cells. Lexeo’s vector technology may allow for lower doses compared with other vector serotypes, company officials said in a recent investor presentation.

LX2006 is designed to address the cardiac effects of FA, a progressive condition affecting an estimated 5,000 people in the United States. The condition often begins between the ages of 10 and 15, and patients can have a combination of neurological and cardiac symptoms. About 80% of FA patients develop cardiomyopathy, which can lead to blood clots, stroke and even death. About 40% of adults with FA have left ventricular hypertrophy, a thickening of the heart’s ventricle walls.

The gene therapy works by delivering a healthy version of the frataxin gene. Frataxin is critical for energy production in cells, and its deficiency leads to progressive damage, particularly in the heart and nervous system.

In clinical studies, 16 participants received a single infusion of the therapy. Six participants had abnormally high levels of left ventricular mass index (LVMI), a measure of heart muscle thickening used as a key trial endpoint. By 12 months, five of those six patients had achieved at least a 10% reduction in LVMI, meeting a primary benchmark set in consultation with the FDA — and five had reached normal LVMI levels.

The treatment also led to a 115% increase in frataxin expression in cardiac tissue in the high-dose cohort. Secondary measures also pointed to clinical benefit: 11 of 12 participants had a marked drop in troponin I, a protein that signals cardiac injury, and most patients showed improvements in functional tests and self-reported outcomes.

The gene therapy was generally well tolerated, with no serious immune reactions or adverse events requiring hospitalization. Only one patient experienced a mild, asymptomatic case of myocarditis a year after dosing.

Related: Gene Therapies for Rare Diseases Twice as Likely to Win FDA Nod, Study Finds

The company said it has secured alignment with the FDA on the design of the pivotal trial and is preparing to launch a concurrent natural history study to serve as a control arm. The planned trial will measure frataxin protein levels and LVMI as co-primary endpoints, with initial efficacy data expected in 2027.

Lexeo’s therapy has already received multiple FDA designations, including Orphan Drug, Fast Track and Regenerative Medicine Advanced Therapy, which could expedite its path to approval. If successful, it would become the first gene therapy approved specifically for FA cardiomyopathy.

“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,” said Lexeo Chief Development Officer Sandi See Tai, M.D., in the news release.