FDA Clears Phase 1/2 Trial of Gene Therapy for FA Heart Disease

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has approved a Phase 1/2 clinical trial for LX2006, Lexeo Therapeutics’ investigational gene therapy for heart disease in people with Friedreich’s ataxia (FA).

Lexeo submitted the trial for approval under an investigational new drug (IND) application based on promising preclinical data. The company expects the trial to begin later this year.

“This IND clearance represents an important milestone for Lexeo,” R. Nolan Townsend, CEO of Lexeo, said in a press release. “Representing our third clinical-stage program overall, LX2006 is also the first disease-modifying, clinical-stage gene therapy treatment for Friedreich’s ataxia and the first clinical-stage program from our cardiovascular gene therapy pipeline.”

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FA is caused by mutations in the FXN gene responsible for making frataxin, a protein important for the proper function of mitochondria — the cell’s energy production centers. These mutations mean that not enough frataxin is produced, which causes damage to nerves and muscles.

The heart is often significantly affected in FA. Cardiomyopathy, an enlargement and weakening of the heart’s muscles affecting its ability to pump blood, is the most common cause of death in FA patients.

LX2006 is a gene therapy designed to deliver a functional frataxin gene to cardiac cells, thereby restoring frataxin levels and improving mitochondrial function. To do this, the gene is packed into a modified and harmless virus called an adeno-associated virus and delivered intravenously (into the vein).

Lexeo’s Phase 1/2 study will be a 52-week, dose-ascending trial of LX2006 in FA patients with cardiomyopathy. The therapy will be given as a one-time intravenous infusion in two dose groups of five patients each.

The FDA’s approval was supported by previous preclinical studies showing that LX2006 safely and effectively improved heart function and survival in a mouse model of FA.

“The potential of LX2006 is supported by our robust preclinical studies showing that LX2006 was able to significantly reverse the cardiac manifestations of the disease, which is the leading cause of death in individuals with Friedreich’s ataxia,” said Jay A. Barth, MD, executive vice president and chief medical officer of Lexeo.

Last year, LX2006 was granted rare pediatric disease and orphan drug designations by the FDA, designations intended to speed progress towards making treatments available for rare diseases.

“We anticipate initiating this Phase 1/2 clinical trial in the middle of this year and look forward to bringing the first potentially disease-modifying gene therapy to patients suffering from FA cardiomyopathy,” said Barth.

Lexeo obtained the rights to LX2006 in 2021 from the therapy’s developer, Adverum Biotechnologies.