IntraBio Inc., announced positive topline data from its pivotal Phase 3 IB1001-303 trial evaluating N-acetyl-L-leucine (levacetylleucine; trade name: Aqneursa) in pediatric and adult patients with ataxia-telangiectasia (A-T), showing statistically significant and clinically meaningful improvements in ataxia severity compared with placebo, meeting both primary and key secondary endpoints.

The randomized, placebo-controlled, double-blind crossover study used the Scale for the Assessment and Rating of Ataxia (SARA) as its primary endpoint; levacetylleucine showed a -1.88-point improvement versus -0.14 with placebo after 12 weeks (p<0.001). Secondary endpoints, including the International Cooperative Ataxia Rating Scale (ICARS) and the Investigator’s Clinical Global Impression of Improvement (CGI-I), also demonstrated statistically significant benefits. The therapy was well tolerated with no drug-related serious adverse events, consistent with its established safety profile.

Research context

A-T is a rare, progressive neurodegenerative disorder caused by mutations in the ATM gene, characterized by cerebellar degeneration, loss of coordination, speech and eye-movement impairments, immune deficiencies, and a markedly elevated cancer risk; there are currently no approved disease-modifying treatments for A-T.

N-acetyl-L-leucine (NALL) is a modified derivative of the essential amino acid leucine that has recently emerged as a promising therapeutic for rare neurodegenerative and lysosomal storage disorders. NALL is believed to act as a neuroprotectant and disease modifier. Preclinical and clinical data suggest it modulates neuronal calcium channels and enhances cerebral glucose metabolism, particularly in the cerebellum, which may underlie its benefits in ataxia and lysosomal storage disorders.

IntraBio secured a first FDA approval for levacetylleucine under the brand name Aqneursa in September 2024, indicated for neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients. The firm is also assessing the molecule for other ultra-rare diseases such as GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases), and multiple sulfatase deficiency, as well as A-T. Based on the IB1001-303 results, IntraBio plans to immediately advance regulatory submissions to the US FDA, the European Medicines Agency, and other global authorities.