Dosing beings in 2nd patient group in Phase 1/2 trial of gene therapy

LX2006 to treat cardiomyopathy by bringing working gene to heart muscle cells

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by Andrea Lobo |

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A first group of patients has been treated with LX2006, an investigational gene therapy for heart disease in people with Friedreich’s ataxia (FA), in a Phase 1/2 clinical trial and dosing has begun in a second group.

LX2006 has been well tolerated and not associated with unexpected safety concerns or toxicity, Lexeo Therapeutics, the treatment’s developer, announced. These findings led the trial’s Data Safety Monitoring Board to support the use of a likely higher, one-time dose in a new group of FA patients with cardiomyopathy.

Initial data from the SUNRISE-FA clinical trial (NCT05445323)’s two groups, including preliminary efficacy findings, are expected in the first half of 2024.

“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, CEO of the Friedreich’s Ataxia Research Alliance, said in a company press release.

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LX2006, Friedreich’s ataxia gene therapy, aims to restore mitochondrial health

FA is caused by mutations in the FXN gene, disrupting the normal production of frataxin, a protein important for the proper function of mitochondria — the cell’s energy production centers. Frataxin deficiency causes damage to nerves and muscles.

Around 75% of all patients develop heart abnormalities, including cardiomyopathy, a disease of the heart muscle that affects its size, shape, thickness, and function.

“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,” Farmer said.

LX2006 is designed to deliver a functional FXN gene to heart muscle cells, increasing frataxin levels and restoring mitochondrial function and energy production. The gene is delivered via a modified and harmless adeno-associated virus (AAV).

SUNRISE-FA is a one-year, dose-ascending, and open-label Phase 1/2 trial evaluating the safety, tolerability, and preliminary efficacy of LX2006 in FA patients with cardiomyopathy. The therapy is administered once by intravenous infusion, and the trial is recruiting eligible patients, ages 18 to 40, at sites in the U.S.

Preliminary efficacy will be assessed through evaluations of cardiac structure and function, as well as cardiac proteins and blood biomarkers.

Long-term safety and LX2006’s early efficacy will continue to be evaluated in patients for four years following their completion of the study’s 52 weeks.

“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,” said R. Nolan Townsend, Lexeo’s CEO.

Preclinical studies, including those in an FA mouse model, found LX2006 safely and effectively improved heart function and survival, with a favorable safety profile, the company reported. These studies supported the U.S. Food and Drug Administration (FDA)’s decision to allow the company to open its gene therapy trial last year.

LX2006 was granted rare pediatric disease and orphan drug designations by the FDA. Both designations are intended to speed the development of new treatments for rare diseases.