Lexeo Therapeutics’ investigational gene therapy reduces left ventricular volume and wall thickness in patients with Friedreich’s ataxia, according to a small study.
Lexeo Therapeutics on Monday posted interim Phase I/II data for its investigational gene therapy LX2006, which significantly lowered hypertrophy in patients with Friedreich’s ataxia.
While promising, the interim readout comes from a small number of patients: Only 11 patients have been dosed with LX2006 so far, of whom four had abnormally high left ventricular mass index (LVMI) at baseline. In three of these patients, the left ventricle shrunk by more than 10% at 12 months, which is a “clinically meaningful threshold of improvement,” Lexeo Chief Development Officer Sandy See Tai said in an investor call on Monday.
LX2006 also showed a “favorable pattern of improvement post-treatment,” See Tai added.
At 12 months, the median reduction in LVMI was 11.4%, while left ventricular lateral wall thickness—known to be an early indicator of ventricular hypertrophy—dropped by 13.6% at this time point. Two patients were followed through 18 months, and their mean LVMI reduction improved by 18.3%.
LX2006 treatment also reflected positively on key biomarkers. Levels of high-sensitivity troponin I, an indicator of myocardial injury, fell by 53.3% on average in all participants at 12 months. Meanwhile, levels of the frataxin protein, which are abnormally reduced in Friedreich’s ataxia, increased in all evaluated patients.
As for safety, the investigational gene therapy was well-tolerated with no treatment-related serious adverse events. Lexeo has likewise not detected signs of complement activation or other signals of immunogenicity, nor has there been evidence of cardiac or hepatic damage. All side effects were transient and none of the patients have dropped out of the study.
“We find these data highly encouraging,” See Tai said during the call, noting that the gene therapy’s effects on lateral wall thickness and troponin I “further highlight the potential therapeutic impact of LX2006. Combined with the LVMI results, the data provide greater confidence of a sustained and consistent overall treatment effect.”
Friedreich’s ataxia is a genetic, progressive and degenerative disorder that affects several systems across the body. The condition is caused by loss-of-function mutations in the frataxin gene, which otherwise plays a critical role in sustaining the normal function of the mitochondria. According to Lexeo’s website, Friedreich’s ataxia afflicts one in every 50,000 people, and 80% of these patients will eventually develop cardiomyopathy.
Packaged in an adeno-associated virus vector, LX2006 is an investigational gene therapy that works by delivering a functional copy of the frataxin gene specifically into myocardial cells, in turn restoring normal mitochondrial function in the heart. Preclinical studies have shown that LX2006 can reverse cardiac abnormalities in disease models, while also having a good overall safety profile.
Lexeo plans to share more details regarding Monday’s interim readout—as well as an additional cardiac biopsy—at an upcoming medical congress, according to the company’s announcement.
