June 15, 2026 —
Lexeo Therapeutics announced that it has finalized the protocol and statistical analysis plan for SUNRISE-FA 2, the pivotal trial intended to support a future Biologics License Application for LX2006, an investigational AAV-based gene therapy for Friedreich’s ataxia cardiomyopathy.
LX2006 is designed to intravenously deliver a functional FXN gene, enabling cells to produce frataxin, the protein that is deficient in Friedreich’s ataxia. Because FA is caused by mutations in a single gene, it is considered a strong candidate for gene therapy approaches that aim to address the disease at the genetic level. Cardiac involvement is a major cause of morbidity in FA, and patients with FA cardiomyopathy remain in need of disease-modifying treatment options.
SUNRISE-FA 2 will be an open-label pivotal study enrolling 13 participants aged 16 years and older who will receive a single intravenous administration of high-dose LX2006 at 1.2×10¹² vector genomes per kilogram, compared with 13 untreated control participants. The untreated control arm will be implemented prospectively under the same protocol and does not include a placebo or sham procedure.
The study’s primary endpoint is left ventricular mass index, or LVMI, measured by cardiac MRI, with a topline efficacy analysis planned at six months post-treatment. The statistical analysis plan is powered to detect an LVMI effect size of at least 15%. Inclusion criteria will focus on participants with abnormal baseline LVMI, defined as at least two standard deviations above the normal mean.
Key secondary endpoints include neurologic and cardiac outcomes and relevant biomarkers, such as the modified Friedreich Ataxia Rating Scale, Kansas City Cardiomyopathy Questionnaire, high-sensitivity troponin-I, and lateral wall thickness. Participants in the untreated control arm will be eligible to cross over to receive LX2006 after six months and will be included in the six-month efficacy analysis and long-term follow-up.
Lexeo said the FDA has recommended removing cardiac frataxin protein expression as a co-primary endpoint, as it is no longer necessary to demonstrate proof of mechanism for LX2006 based on clinically meaningful Phase 1/2 results observed to date. The FDA has also confirmed that no additional nonclinical bridging studies are required.
From a manufacturing perspective, Lexeo may use its optimized, high-yield Sf9-baculovirus final manufacturing process to initiate dosing in SUNRISE-FA 2. Clinical drug product has already been manufactured at commercial scale and is available for patient dosing. The company also noted that its BLA-supportive manufacturing strategy includes flexible process validation, including reduced PPQ manufacturing batches.
The pivotal study remains on track to initiate in the second quarter of 2026, with the first patient expected to be enrolled by the end of June. Lexeo expects a topline data readout in the second half of 2027 and a BLA submission under the accelerated approval pathway in the first half of 2028.
The company is also conducting CLARITY-FA, a natural history study designed to provide supportive evidence on the untreated disease course for both accelerated and full approval. CLARITY-FA shares identical inclusion criteria with SUNRISE-FA 2, and enrolled patients may be eligible to participate in the pivotal study.
If successful, LX2006 could become one of the most advanced AAV gene therapy programs targeting the cardiac manifestations of Friedreich’s ataxia and may provide a potential disease-modifying option for patients with FA cardiomyopathy.
