news

한어Русский языкEnglishFrançaisIndonesianSanskrit日本語DeutschPortuguêsΕλληνικάespañolItalianoSuomalainenLatina

In two clinical trials, Lexeo Therapeutics' Friedreich Ataxia (FA) cardiomyopathy gene therapy LX2006 was well tolerated, with no serious adverse events related to treatment, and clinically meaningful improvements in cardiac biomarkers. However, the impact on patients' lives still needs further evaluation.

On July 15, 2024, local time, Lexeo Therapeutics, a US company, announced the latest progress of its Friedreich Ataxia (FA) cardiomyopathy gene therapy LX2006: In a Phase 1/2 clinical trial and a Phase 1a clinical trial initiated by researchers from Weill Cornell Medicine in the United States, LX2006 was well tolerated, with no serious adverse events related to treatment, and clinically significant improvements in cardiac biomarkers, which increased over time.

Friedreich's ataxia is an inherited, progressive, degenerative, multisystem disease caused by mutations in the FXN gene that disrupt the normal production of the frataxin protein, which is essential for the function of mitochondria in cells and the maintenance of heart function. Its loss leads to damage to the peripheral nerves and parts of the brain that control movement and balance, resulting in neurological symptoms, including impaired muscle coordination or ataxia, which worsen over time. As the disease progresses, patients often develop various heart diseases, including thickening of the heart muscle or hypertrophic cardiomyopathy and arrhythmias.

On February 28, 2024, the U.S. Food and Drug Administration (FDA) approved Skyclarys, the first prescription drug for the treatment of Friedreich's ataxia in patients over the age of 16, but there is currently no drug in the world to treat Friedreich's ataxia cardiomyopathy.

According to Lexeo's announcement, LX2006 is an adeno-associated virus (AAV)-based gene therapy candidate for the treatment of Friedreich's ataxia cardiomyopathy by intravenous injection. It can deliver a functional frataxin gene, promote the expression of frataxin protein and restore mitochondrial function in cardiomyocytes.

The data published this time include records of 8 participants, who were followed by researchers for at least 6 months. The data showed that the expression level of FXN protein increased in patients who could be evaluated. At the beginning of the study, 4 subjects had an elevated left ventricular mass index (LVMI), and 3 of them had a reduction of more than 10% in left ventricular mass index (LVMI) (a marker of heart disease morbidity and mortality, with a normal value of less than 50%) at 12 months. The researchers also observed a reduction in lateral wall thickening (an early indicator of heart dysfunction) and a reduction in biomarkers of myocardial damage.

In April 2024, Lexeo announced that the FDA has granted LX2006 rare pediatric disease designation, fast track designation, and orphan drug designation for the treatment of FA cardiomyopathy.

According to biopharmaceutical industry media Fierce Biotech, Lexeo is trying to use VO2 max to evaluate the drug's impact on patients' lives. VO2 max refers to the maximum amount of oxygen that the body can absorb and use during exercise, and is an indicator of cardiopulmonary fitness. The data showed that the peak VO2 of 3 of the 8 participants could not reach a level that could be reliably interpreted, while the values ​​of the other 5 subjects improved by an average of 1% after 6 months and an average of 4% after 12 months. Lexeo will continue to evaluate peak VO2 in its research and is exploring other cardiopulmonary exercise testing methods that may be more useful for the patient population.

These data mean that the evidence supporting LX2006 comes solely from cardiac evaluations. Lexeo said there are precedents for drugs being approved for LVMI or transgene expression. Based on these results, Lexeo plans to accelerate the development of the therapy, including discussions with regulators on the design of a pivotal trial and applying for potential accelerated approval.

Fierce Biotech reported that Skyclarys has only shown efficacy in neurological indicators, while LX2006 targets cardiac indicators, which distinguishes the two, but the market may become more competitive in the coming years. Voyager Therapeutics and Neurocrine Biosciences are studying FXN gene therapy, Solid Biosciences and Lacerta Therapeutics are also working on gene therapy, and Prime Medicine and Tune Therapeutics have early-stage gene editing programs.

References:

1.https://www.fiercebiotech.com/biotech/lexeo-links-gene-therapy-improvements-rare-heart-disease-disappoints-investors

2.https://www.lexeotx.com/programs/cardiac-programs/friedreichs-ataxia/

3.https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-phase-12-clinical