Treatment with levacetylleucine significantly improves ataxia symptoms in paediatric and adult patients with ataxia-telangiectasia (A-T) compared with placebo, according to the phase III IB1001-303 trial presented at AAN 2026.
Overall, the study met its primary and key secondary endpoints by demonstrating statistically significant improvements in the Scale for the Assessment and Rating of Ataxia (SARA) score and the International Cooperative Ataxia Rating Scale (ICARS) and investigator’s Clinical Global Impression of Improvement (CGI-I), respectively, in this patient population, said Patterson.
The researchers conducted a global, double-blind, placebo-controlled, crossover study involving 73 participants, including 47 children and 26 adults, with a genetically confirmed diagnosis of A-T. Participants were assigned to one of two treatment sequences, wherein levacetylleucine was administered for 12 weeks, followed by placebo for 12 weeks in the first sequence, and vice versa in the second sequence. Levacetylleucine 2–4 g/day was administered as granules dissolved in orange juice, water, or almond milk, with dosing based on weight.
After 12 weeks of treatment, patients who received levacetylleucine had a statistically significant and clinically meaningful 1.88-point improvement in the SARA score compared with those on placebo (−1.92 vs −0.14; between-group difference, −1.88; p<0.001). [AAN 2026, abstract 001]
Furthermore, this improvement was evident even when both treatment sequences were analysed together, showing a benefit with levacetylleucine over the 12-week treatment period, according to study author Dr Marc Patterson from IntraBio Inc., Austin, Texas, US.
The levacetylleucine group also achieved a 2.84-point improvement in the ICARS (mean change from baseline, −4.22 vs −1.69; p=0.003) and a 0.4-point improvement in the CGI-I (mean change from baseline, −0.6 vs −0.2; p=0.02) compared with the placebo group.
These secondary endpoints, including ICARS and CGI-I, provided supportive evidence for the primary endpoint, noted Patterson.
In terms of safety, the rates of adverse events (AEs) were comparable between the levacetylleucine and placebo groups, with no drug-related serious AEs or deaths occurring in either group. There were also no treatment-emergent AEs reported in >10 percent of levacetylleucine-treated patients.
Safety findings indicated that levacetylleucine was safe and well-tolerated, which was consistent with the established safety profile, Patterson noted.
“Overall, levacetylleucine demonstrated a significant benefit vs placebo, and clinically meaningful improvements in neurological manifestations of A-T, functioning, and quality of life, and a favourable benefit-risk profile for the treatment of A-T,” said Patterson.
The ongoing extension phase will provide further insights into long-term efficacy and safety, with regulatory submissions anticipated in the US, Europe, and other jurisdictions, potentially enabling the approval of levacetylleucine as the first approved therapy for A-T, he added.