LX2006 designated breakthrough therapy for FA cardiomyopathy
Gene therapy also selected for pilot program to speed development
The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to LX2006, a gene therapy for cardiomyopathy in Friedreich’s Ataxia (FA).
The status means the Lexeo Therapeutics candidate may be eligible for fast track review and extra FDA guidance during the regulatory process, which could help the treatment reach patients more quickly if it proves to be safe and effective.
“Receiving Breakthrough Therapy designation is a significant milestone, highlighting the potential of LX2006 and the strength of clinical evidence generated to date,” Sandi See Tai, MD, chief development officer of Lexeo, said in a company press release. “We are highly encouraged by the impact of LX2006 on key measures of cardiac health, especially given the lack of treatments for FA cardiomyopathy today, which is the leading cause of death in FA.”
Breakthrough therapy designation signifies that LX2006 may provide a substantial improvement over existing therapies for a serious condition. Cardiomyopathy, a thickening of the heart muscle that impairs blood pumping, is a common and serious symptom of FA. Currently, Skyclarys (omaveloxolone) is the only approved FA treatment, but it does not directly address cardiac symptoms.
The FDA also selected LX2006 to participate in the Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP), a program designed to help expedite drug development and make medications available to patients sooner.
Treatment aims to deliver functional gene copy to cells
FA is a rare genetic disorder marked by progressive ataxia, a loss of muscle coordination and control. Over time, people with FA may experience symptoms affecting the nerves and muscles, such as difficulty speaking and serious heart issues like cardiomyopathy.
These symptoms are caused by mutations in the FXN gene, which provides instructions for making frataxin, a protein essential for cellular energy production. When frataxin levels are low, as in FA, energy production in the cells becomes impaired, leading to cellular damage. Nerve and muscle cells are especially vulnerable because they require large amounts of energy to function properly.
LX2006 aims to correct this frataxin deficit by delivering a package containing a functional copy of FXN to heart cells. A viral vector, engineered so as not to cause disease in humans, carries this cargo. The medication is administered through into-the-vein (intravenous) infusion.
Two ongoing clinical trials are testing the treatment’s safety and efficacy in people with FA. Lexeo is sponsoring the Phase 1/2 SUNRISE-FA study (NCT05445323), and investigators at Cornell initiated a separate Phase 1 study (NCT05302271). Both focus on adults ages 18-50, and the latter is actively recruiting in New York.
Initial efficacy data from the two studies showed that participants have generally tolerated the therapy well, with none reporting severe adverse events, and have improved in several cardiac function measures. The left ventricular mass index (LVMI), which measures enlargement of the heart’s main pumping chamber, has stayed within the normal range for most participants. Five of the six patients who began the trial with abnormally elevated LVMI had reached the normal range by their most recent visits.
Biopsies of heart tissue demonstrated increased frataxin levels three months after treatment. Participants on higher doses of LX2006 tended to have greater increases.
“We are also optimistic about the improvements we have observed in functional measures of FA more broadly,” See Tai said. Most participants had improved scores on the modified Friedreich’s Ataxia Rating Scale (mFARS), a measure of physical impairment, rather than heart function.
Lexeo is planning a registrational study of LX2006, expected to begin by early 2026. The trial will enroll 12-16 adults with FA and abnormal LVMI, along with smaller groups of adolescents and children. Adult participants will receive the highest dose of LX2006 that was previously tested.
The study aims to measure frataxin protein levels after three months and changes in LVMI after one year. In collaboration with the FDA, Lexeo has set a goal of achieving at least a 10% improvement in LVMI as one of the trial’s primary endpoints.
An observational study, CLARITY-FA (NCT06865482), will serve as the external control group for the registrational trial. CLARITY-FA is currently recruiting participants ages 6 and older with FA-associated cardiomyopathy at a site in St. Louis.
“We look forward to a continued partnership with the FDA through the Breakthrough Therapy designation and the CDRP program as we work to bring this potential treatment to patients as quickly as possible,” See Tai said.
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