Trial testing gene therapy for FA cardiomyopathy set to start soon
Lexeo aims to seek FDA accelerated approval for treatment
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A Phase 2 clinical trial testing Lexeo Therapeutics’ gene therapy LX2006 in people with Friedreich’s ataxia (FA) and the heart condition cardiomyopathy expects to enroll its first participant by the end of the month, the company said.
The SUNRISE-FA 2 study is a pivotal trial, with data expected to support an application to U.S. regulators seeking accelerated approval of the therapy in 2028.
“We have reached a major milestone with the finalization of the SUNRISE‑FA 2 pivotal study design, establishing a clear and rigorous path to evaluate LX2006 in [FA] cardiomyopathy,” Narinder Bhalla, MD, chief medical officer for Lexeo, said in a company press release. “This progress brings us one step closer to delivering a potential new therapy.”
FA is caused by mutations in the FXN gene that lead to a loss of frataxin, a protein important for cellular energy production. Cells consequently don’t have the energy they need to function, and they ultimately become damaged. Nerve and muscle cells, which have high energy demands, are particularly vulnerable.
While the hallmark symptom of FA is ataxia (a loss of voluntary muscle control), most people also develop hypertrophic cardiomyopathy, in which the heart muscles become thickened and enlarged, making it harder to pump blood.
Addressing cardiomyopathy
No approved treatments for FA directly address the disease’s cardiac symptoms. LX2006, given by a one-time infusion into the bloodstream, is designed to deliver a working version of FXN directly to heart cells, enabling them to produce more frataxin.
Interim data from two trials involving adults with FA — the Lexeo-sponsored Phase 1/2 SUNRISE-FA study (NCT05445323) and an investigator-initiated Phase 1 study (NCT05302271) — showed that the therapy had beneficial effects on heart function.
Five of six people with an elevated left ventricular mass index (LVMI), which indicates that heart’s main pumping chamber is thickened and enlarged, achieved an LVMI measurement within the normal range after gene therapy. Others with a normal LVMI showed improvements or stabilization over time.
SUNRISE-FA 2 will initially enroll 26 people with FA, ages 16 and older, with abnormal LVMI. Half of them will receive a single infusion of high-dose LX2006, while the other half will serve as an untreated control group.
Unlike many other clinical trials, the untreated control group won’t receive a placebo or sham procedure to mimic the administration approach. This will be more reflective of the natural history of the disease — that is, what would happen in real life if a person wasn’t treated — according to Lexeo.
Including the untreated group in the trial design rather than relying on an external natural history study helps ensure consistency in methodology and evaluation methods.
The study’s main goal will be to evaluate changes in LVMI using cardiac MRI imaging after six months. Other measures of neurological and cardiac health will also be evaluated.
After six months, participants in the untreated arm will be able to receive LX2006. If deemed safe after the first group of participants, the study may also dose a group of younger children with FA.
The Friedreich’s Ataxia Research Alliance (FARA) applauded the announcement.
“FARA congratulates [Lexeo] on this important milestone,” said Jennifer Farmer, the association’s CEO. “We commend Lexeo for designing SUNRISE-FA 2 with scientific rigor while recognizing that a sham or placebo design is neither necessary nor appropriate in the context of gene therapy and adding a pediatrics arm to this study, putting patients first as we work urgently toward the first approved treatment for FA cardiomyopathy.”
Top-line trial data are expected in the second half of next year.
Lexeo intends to seek approval of LX2006 under an accelerated approval pathway, which allows a therapy to be conditionally marketed based on preliminary evidence that it will be of benefit for patients. Additional clinical trial data confirming these benefits are needed to secure full approval.
The company is in talks with the FDA about what confirmatory evidence will be needed. It may include certain one-year data from SUNRISE-FA 2. Supportive natural history data will also come from the observational study CLARITY-FA (NCT06865482), which is recruiting FA patients, ages 6 and older, at sites in the U.S., Brazil, Canada, and Europe.
