Lexeo's gene therapy shows promise for Friedreich's ataxia cardiomyopathy

Lexeo Therapeutics’ investigational gene therapy is showing promise as a treatment for Friedreich’s ataxia (FA) cardiomyopathy, according to new phase 1/2 data released by the company.

Friedreich’s ataxia (FA) is a neurodegenerative movement disorder and the most prevalent form of inherited ataxia, affecting approximately one in every 40,000 people. The disease typically manifests between the ages of ten and 15. Early symptoms include unsteady posture, frequent falls, fatigue, and progressive difficulty in walking due to impaired coordination of voluntary movements.

The investigational therapy, named LX2006, is administered intravenously and targets FA cardiomyopathy, which is the leading cause of death among FA patients. The therapy has demonstrated clinically meaningful improvements in cardiac biomarkers in patients participating in both the Lexeo SUNRISE-FA phase 1/2 trial and the Weill Cornell Medicine investigator-initiated phase 1A study. Notably, these improvements have been observed to increase over time.

One significant finding from the trials is a mean reduction in left ventricular mass index (LVMI) by 11.4% at 12 months among patients who had elevated LVMI at the start of the study. This reduction further increased to 18.3% at 18 months. Additionally, left ventricular lateral wall thickness, an early marker of left ventricular hypertrophy, decreased by 13.6%. Troponin I, a biomarker indicative of myocardial injury, showed an average reduction of 53.3% across all patients at the 12-month mark. Furthermore, an increase in frataxin—a protein deficient in FA—was observed in all patients. Importantly, LX2006 was well tolerated by participants in the studies.

Dr. Sandi See Tai, Chief Development Officer at Lexeo, noted that these findings, along with the increases in frataxin protein expression observed in SUNRISE-FA cardiac biopsies, emphasize the potential of LX2006 to improve outcomes for individuals with FA cardiomyopathy.

The investigational therapy LX2006 has already received rare pediatric disease, fast track, and orphan drug designations from the U.S. Food and Drug Administration (FDA) specifically for the treatment of FA cardiomyopathy. Dr. Eric Adler, Chief Medical Officer and Head of Research at Lexeo, expressed optimism about the data, stating that they are greatly encouraged by the potential of LX2006 to treat FA cardiomyopathy, a severe and life-threatening condition that currently has no approved therapies. Dr. Adler also highlighted the favorable safety profile and the clinical benefits observed thus far, suggesting that there is potential for expedited clinical development and possibly accelerated approval of this treatment.

Overall, the early data from the phase 1/2 trials indicate that Lexeo’s LX2006 gene therapy might offer a significant advancement in the treatment of FA cardiomyopathy, providing hope for a condition that presently lacks effective treatments.