The first FDA-approved treatments for rare ataxia disorders have entered clinical use within the past year, though supportive care remains the standard for most patients. In February 2023, Omaveloxolone became the first therapy approved for Friedreich ataxia (FA) in patients aged 16 and older. More recently, the FDA approved levacetylleucine for ataxia-telangiectasia (A-T), marking the first treatment option for this patient group after a phase 3 trial demonstrated a 1.9-point improvement on the Scale for the Assessment and Rating of Ataxia (SARA) compared to placebo—a result deemed statistically significant.
Not all recent developments have been successful. Quince Therapeutics discontinued development of dexamethasone sodium phosphate encapsulated in erythrocytes (eDSP) for A-T in January 2026 after its phase 3 trial failed to meet primary or secondary endpoints. In spinocerebellar ataxia (SCA), the FDA declined to approve troriluzole in November 2025, citing concerns about real-world evidence studies and potential bias. The company has since refocused its late-stage pipeline on other programs.
New protein replacement and gene therapies in development
Despite these setbacks, six investigational programs highlight a growing pipeline for ataxia treatments. In Friedreich ataxia, nomlabofusp (CTI-1601), a protein replacement therapy, received breakthrough therapy designation from the FDA in February 2026. Administered via daily subcutaneous injection, the drug aims to restore frataxin (FXN) levels in patients with FXN deficiency. Updated data from an open-label extension study showed mean skin FXN concentrations increasing from 3.7 pg/µg at baseline to 12.1 pg/µg after one year, with all evaluable participants exceeding FXN levels observed in asymptomatic carriers.
The clinical benefit was modest but notable: 13 participants treated for a year showed a 1.0-point improvement in the modified Friedreich Ataxia Rating Scale (mFARS), compared to a 1.6-point worsening in a matched reference group. However, safety concerns emerged as 10 participants discontinued treatment due to anaphylaxis, though all recovered with standard care. Larimar Therapeutics submitted the first module of a rolling biologics license application (BLA) in June 2026, seeking accelerated approval. A global phase 3 study is scheduled to begin in the third quarter of 2026, with the Upright Stability Score as its primary endpoint.
A separate approach addresses the cardiomyopathy responsible for most FA-related deaths. LX2006 (AAVrh.10hFXN), a gene therapy from Lexeo Therapeutics, delivers a functional FXN gene directly to cardiomyocytes. Phase 1/2 results published in June 2026 showed reductions in left ventricular mass index (LVMI) and high-sensitivity troponin I across 17 patients, alongside up to a 123% increase in cardiac frataxin levels in biopsy samples. The key SUNRISE-FA 2 trial began enrolling in June 2026, randomizing 26 participants to high-dose LX2006 or an untreated control arm. Topline data are expected in late 2027, with an accelerated approval BLA submission planned for early 2028.
Gene therapy targets FA’s deadliest complication
The trial design avoids placebo or sham controls, instead allowing control participants to cross over to treatment after six months. Lexeo’s approach reflects a broader shift toward real-world efficacy assessments in progressive diseases where natural history data are limited.
While nomlabofusp and LX2006 use different mechanisms—protein replacement versus gene delivery—their shared focus on FXN restoration highlights a major gap in current FA care. Omaveloxolone, the only approved FA therapy, does not target cardiomyopathy, the leading cause of death in these patients. Early phase 3 results for LX2006 suggest even modest improvements in cardiac function could translate into meaningful survival benefits, though long-term data remain pending.
The FDA’s acceptance of skin FXN concentration as a surrogate endpoint for nomlabofusp reflects a broader trend: regulatory agencies are increasingly open to novel biomarkers in rare diseases where traditional clinical measures are inadequate. This flexibility could accelerate approvals for other ataxia therapies if they demonstrate consistent biological effects.
SCA pipeline faces unique genetic and trial hurdles
The pipeline for spinocerebellar ataxias (SCAs) presents distinct challenges. Unlike Friedreich ataxia, where genetic and biochemical pathways are better defined, SCAs encompass over 40 subtypes with varying mechanisms. Two programs stand out: VO659, an antisense oligonucleotide from Vico Therapeutics, and the repurposed drug fampridine (4-aminopyridine) for SCA27B.
VO659 targets expanded CAG repeats in mutant transcripts, a strategy previously tested in Huntington disease. Interim pharmacodynamic data from Huntington patients showed a 38% reduction in mutant huntingtin after four months of dosing. The trial has since adjusted to a twice-annual dosing regimen, with the first U.S. sites cleared in February 2026. Radiculitis, a known side effect, has been reported in multiple participants, but the company remains optimistic about its basket trial design, which includes SCA1 and SCA3 alongside Huntington disease.
For SCA27B, an intronic GAA repeat expansion in FGF14 has emerged as a treatable target. Observational data on fampridine, already approved for multiple sclerosis, showed 86% of treated patients reporting daily living improvements, with some experiencing marked reductions in symptom severity during on/off trials. A phase 3 study (NCT07185347) is now enrolling participants, though regulatory pathways for repurposed drugs in rare ataxias remain uncertain.
