Lexeo's Gene Therapy for Friedreich's Ataxia Shows Promise in Phase I/II Trial

Lexeo Therapeutics has unveiled compelling data from its Phase I/II trial of LX2006, a gene therapy candidate for Friedreich's ataxia cardiomyopathy. The results, which demonstrate significant improvements in cardiac function and biomarkers, have paved the way for the company to advance towards pivotal trials.

Promising Cardiac Outcomes

LX2006 showed a marked impact on cardiac health in patients with Friedreich's ataxia cardiomyopathy. In a cohort of six patients with abnormal left ventricular mass index (LVMI) at baseline, treatment with LX2006 resulted in a 25% mean improvement in LVMI at 12 months or sooner. Notably, five of the six patients reached normal LVMI measurements by their latest visit.

The therapy's effects extended beyond LVMI improvements. Among 12 patients followed for at least six months, 10 experienced reductions in lateral wall thickness, while 11 demonstrated a more than 25% drop in high-sensitivity troponin I levels. These outcomes suggest a broad impact on cardiac health markers.

Dose-Dependent Effects and Biomarker Improvements

Lexeo reported that LX2006's effects appeared to be dose-dependent, a critical factor in determining optimal treatment regimens. The gene therapy also showed promise in addressing the underlying molecular deficits of Friedreich's ataxia. Cardiac frataxin, a protein typically under-expressed in the condition, increased in a dose-dependent manner three months post-treatment.

Stifel analysts, commenting on the results, noted that the impact on frataxin levels was "encouraging" and that effects on other relevant biomarkers "corroborate the efficacy signal." This molecular evidence adds weight to the clinical observations and supports the potential mechanism of action for LX2006.

Path to Pivotal Trials

Buoyed by these results, Lexeo is now charting a course for pivotal trials. The company plans to initiate a registrational study by early 2026, with an efficacy readout anticipated in 2027. Stifel analysts view the proposed co-primary endpoints favorably and believe Lexeo has a "solid chance at success."

However, the analysts also noted some uncertainty in the regulatory landscape, particularly in light of recent changes at the FDA. The departure of Peter Marks, former head of the FDA's Center for Biologics Evaluation and Research (CBER), has raised questions about the agency's approach to gene therapies for rare diseases. Marks was known for championing accelerated approvals in this area, and it remains to be seen how his exit might affect regulatory flexibility moving forward.

Despite these uncertainties, Stifel suggested that the dynamics surrounding rare disease treatments are "probably less likely to change," potentially offering some reassurance for companies like Lexeo operating in this space.